{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts directly mention MIR3182, the collective body of work illustrates a broad landscape of immune‐regulatory mechanisms in which microRNAs are known to play critical roles. Many studies here detail how the generation, expansion, and function of CD4⁺ regulatory T cells (Tregs) and helper T cell populations are exquisitely controlled by extracellular cytokine cues (such as IL‑2, TGF‑β, and IFN‑γ), transcription factors, chromatin remodeling complexes, and post‐transcriptional regulatory processes. Given that loss of miRNA processing (for example, in Dicer‐deficient models) disrupts Treg‐mediated tolerance, it is plausible by analogy that individual microRNAs—including MIR3182—could fine‐tune key signaling pathways required for T cell development and immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMany of these reports emphasize the precise regulation of T cell lineage commitment, activation, and suppression via interplay between surface receptors and intracellular factors. They describe how epigenetic mechanisms—ranging from silencer and enhancer functions to chromatin remodelers like Mi‑2β—and the balance of costimulatory versus inhibitory signals underlie proper CD4 expression and Treg function. In this complex regulatory network, post‐transcriptional modulation by microRNAs is emerging as a critical determinant of cellular fate. By extension, although not explicitly examined in these studies, MIR3182 may act to modulate the stability or translation of mRNAs that encode proteins essential for T cell receptor signaling, Treg suppressive capacity, or the maintenance of immune tolerance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional integrative analyses accentuate the role of the miRNA processing machinery in securing immune tolerance. Data from Dicer‐deficient mouse models, for instance, have underscored that the absence of mature microRNAs critically impairs the suppressive function of natural CD4⁺Foxp3⁺ regulatory T cells. This finding opens the possibility that specific microRNAs—MIR3182 among them—could target transcription factors or signaling mediators to modulate the balance between effector and regulatory T cell responses across contexts such as autoimmunity, inflammation, transplant tolerance, and tumor immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "49"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, while direct experimental evidence for MIR3182 is not presented in these works, the overarching themes demonstrate that microRNAs—and by extrapolation MIR3182—are likely to play an important regulatory role in fine‐tuning gene expression programs that control T cell activation, lineage commitment, and immunological tolerance. Future targeted investigations will be required to identify the specific mRNA targets and signaling pathways modulated by MIR3182 in the context of T cell–mediated immune responses.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "R K Leung, K Thomson, A Gallimore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni733"}], "href": "https://doi.org/10.1038/ni733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11694883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11694883"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thomas R Malek, Aixin Yu, Vladimir Vincek, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(02)00735-9"}], "href": "https://doi.org/10.1016/s1097-2765(02"}, {"type": "t", "text": "00735-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12453416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12453416"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Eugenio Stabile, Mary Susan Burnett, Craig Watkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.CIR.0000079225.50817.71"}], "href": "https://doi.org/10.1161/01.CIR.0000079225.50817.71"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12821542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12821542"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Elizabeth A Lynch, Claudia A W Heijens, Noah F Horst, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: IL-16/CD4 preferentially induces Th1 cell migration: requirement of CCR5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.171.10.4965"}], "href": "https://doi.org/10.4049/jimmunol.171.10.4965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14607889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14607889"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Aaron J Tyznik, Joseph C Sun, Michael J Bevan "}, {"type": "b", "children": [{"type": "t", "text": "The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20031961"}], "href": "https://doi.org/10.1084/jem.20031961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14769854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14769854"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Christine J Williams, Taku Naito, Pablo Gómez-Del Arco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2004.05.005"}], "href": "https://doi.org/10.1016/j.immuni.2004.05.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15189737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15189737"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xinghua Zhou, Anna-Karin L Robertson, Mats Rudling, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20041959"}], "href": "https://doi.org/10.1084/jem.20041959"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15753203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15753203"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Linda Fahlén, Simon Read, Leonid Gorelik, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Essential role for interleukin-2 for CD4(+)CD25(+) T regulatory cell development during the neonatal period."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20041179"}], "href": "https://doi.org/10.1084/jem.20041179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15753210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15753210"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Reginald M Gorczynski, Lydia Lee, Ivo Boudakov "}, {"type": "b", "children": [{"type": "t", "text": "Augmented Induction of CD4+CD25+ Treg using monoclonal antibodies to CD200R."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transplantation (2005)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15880066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15880066"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hiroyoshi Nishikawa, Takuma Kato, Isao Tawara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Accelerated chemically induced tumor development mediated by CD4+CD25+ regulatory T cells in wild-type hosts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0503852102"}], "href": "https://doi.org/10.1073/pnas.0503852102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15961541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15961541"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Divya J Mekala, Rajshekhar S Alli, Terrence L Geiger "}, {"type": "b", "children": [{"type": "t", "text": "IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+ T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0505445102"}], "href": "https://doi.org/10.1073/pnas.0505445102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16087867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16087867"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Vladimir R Ramirez-Carrozzi, Aaron A Nazarian, Caiyi C Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1383206"}], "href": "https://doi.org/10.1101/gad.1383206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16452502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16452502"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "R Fujii, T Kanai, Y Nemoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FTY720 suppresses CD4+CD44highCD62L- effector memory T cell-mediated colitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00496.2005"}], "href": "https://doi.org/10.1152/ajpgi.00496.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16574986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16574986"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Haiying Liu, Mousa Komai-Koma, Damo Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0601554103"}], "href": "https://doi.org/10.1073/pnas.0601554103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16632602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16632602"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Zhaojun Wang, Jian Hong, Wei Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI25826"}], "href": "https://doi.org/10.1172/JCI25826"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16906223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16906223"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Patrick T Walsh, Jodi L Buckler, Jidong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTEN inhibits IL-2 receptor-mediated expansion of CD4+ CD25+ Tregs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI28057"}], "href": "https://doi.org/10.1172/JCI28057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16917540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16917540"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Renu Garg, Ignacio J Juncadella, Nandhini Ramamoorthi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: CD4 is the receptor for the tick saliva immunosuppressor, Salp15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.177.10.6579"}], "href": "https://doi.org/10.4049/jimmunol.177.10.6579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17082567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17082567"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Catherine Q Nie, Nicholas J Bernard, Louis Schofield, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD4+ CD25+ regulatory T cells suppress CD4+ T-cell function and inhibit the development of Plasmodium berghei-specific TH1 responses involved in cerebral malaria pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.01783-06"}], "href": "https://doi.org/10.1128/IAI.01783-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17325053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17325053"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Anita Sapoznikov, Jens A A Fischer, Tami Zaft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Organ-dependent in vivo priming of naive CD4+, but not CD8+, T cells by plasmacytoid dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20062373"}], "href": "https://doi.org/10.1084/jem.20062373"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17646404"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17646404"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Kathryn F Wildt, Guangping Sun, Baerbel Grueter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcription factor Zbtb7b promotes CD4 expression by antagonizing Runx-mediated activation of the CD4 silencer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.179.7.4405"}], "href": "https://doi.org/10.4049/jimmunol.179.7.4405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17878336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17878336"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Adina Kay Knight, Ana Belén Blázquez, Shu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD4 T cells activated in the mesenteric lymph node mediate gastrointestinal food allergy in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00323.2007"}], "href": "https://doi.org/10.1152/ajpgi.00323.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17916645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17916645"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Taku Naito, Pablo Gómez-Del Arco, Christine J Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antagonistic interactions between Ikaros and the chromatin remodeler Mi-2beta determine silencer activity and Cd4 gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2007.09.008"}], "href": "https://doi.org/10.1016/j.immuni.2007.09.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17980631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17980631"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Olivier Joffre, Thibault Santolaria, Denis Calise, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1688"}], "href": "https://doi.org/10.1038/nm1688"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18066074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18066074"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "John Andersson, Dat Q Tran, Marko Pesu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20080308"}], "href": "https://doi.org/10.1084/jem.20080308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18710931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18710931"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Guoping Jiang, Horng-Ren Yang, Lianfu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatic stellate cells preferentially expand allogeneic CD4+ CD25+ FoxP3+ regulatory T cells in an IL-2-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transplantation (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/TP.0b013e31818bfd13"}], "href": "https://doi.org/10.1097/TP.0b013e31818bfd13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19077880"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19077880"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Sanhong Yu, Danny Bruce, Monica Froicu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0808700106"}], "href": "https://doi.org/10.1073/pnas.0808700106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19095793"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19095793"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Zhuoxiao Cao, Akm Khyrul Wara, Basak Icli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kruppel-like factor KLF10 targets transforming growth factor-beta1 to regulate CD4(+)CD25(-) T cells and T regulatory cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.000059"}], "href": "https://doi.org/10.1074/jbc.M109.000059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19602726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19602726"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Tomohisa Okamura, Keishi Fujio, Mihoko Shibuya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD4+CD25-LAG3+ regulatory T cells controlled by the transcription factor Egr-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0906872106"}], "href": "https://doi.org/10.1073/pnas.0906872106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19666526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19666526"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Lie Wang, Rémy Bosselut "}, {"type": "b", "children": [{"type": "t", "text": "CD4-CD8 lineage differentiation: Thpok-ing into the nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0901041"}], "href": "https://doi.org/10.4049/jimmunol.0901041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19696430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19696430"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Rudragouda Channappanavar, Brandon S Twardy, Pratima Krishna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Advancing age leads to predominance of inhibitory receptor expressing CD4 T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mech Ageing Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mad.2009.08.006"}], "href": "https://doi.org/10.1016/j.mad.2009.08.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19715717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19715717"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Franco R D'Alessio, Kenji Tsushima, Neil R Aggarwal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI36498"}], "href": "https://doi.org/10.1172/JCI36498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19770521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19770521"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Heiko F Stahl, Tanja Fauti, Nina Ullrich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0007158"}], "href": "https://doi.org/10.1371/journal.pone.0007158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19777054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19777054"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Mark M W Chong, Natalie Simpson, Maria Ciofani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1901610"}], "href": "https://doi.org/10.1101/gad.1901610"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20360383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20360383"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Seng-Ryong Woo, Nianyu Li, Tullia C Bruno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential subcellular localization of the regulatory T-cell protein LAG-3 and the coreceptor CD4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.200939874"}], "href": "https://doi.org/10.1002/eji.200939874"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20391435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20391435"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Ruijiang Song, David Franco, Chia-Ying Kao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00453-10"}], "href": "https://doi.org/10.1128/JVI.00453-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20463063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20463063"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Hyojung Lee, Dukhee Nho, Hwan-Suck Chung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ki.2010.139"}], "href": "https://doi.org/10.1038/ki.2010.139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20463654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20463654"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Xiaofeng Sun, Yan Wu, Wenda Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD39/ENTPD1 expression by CD4+Foxp3+ regulatory T cells promotes hepatic metastatic tumor growth in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2010.05.007"}], "href": "https://doi.org/10.1053/j.gastro.2010.05.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20546740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20546740"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Agustina Tri Endharti, Yusuke Okuno, Zhe Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD8+CD122+ regulatory T cells (Tregs) and CD4+ Tregs cooperatively prevent and cure CD4+ cell-induced colitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1000800"}], "href": "https://doi.org/10.4049/jimmunol.1000800"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21098236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21098236"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Shin Foong Ngiow, Bianca von Scheidt, Hisaya Akiba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-11-0096"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-0096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21430066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21430066"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Koichi Ito, Stephen J Ralph "}, {"type": "b", "children": [{"type": "t", "text": "Inhibiting galectin-1 reduces murine lung metastasis with increased CD4(+) and CD8 (+) T cells and reduced cancer cell adherence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Metastasis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10585-012-9471-7"}], "href": "https://doi.org/10.1007/s10585-012-9471-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22484915"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22484915"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Ekaterina Yurchenko, Marina T Shio, Tony C Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammation-driven reprogramming of CD4+ Foxp3+ regulatory T cells into pathogenic Th1/Th17 T effectors is abrogated by mTOR inhibition in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0035572"}], "href": "https://doi.org/10.1371/journal.pone.0035572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22545118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22545118"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Yu Yu, Hyun-Ii Cho, Dapeng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adoptive transfer of Tc1 or Tc17 cells elicits antitumor immunity against established melanoma through distinct mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1201989"}], "href": "https://doi.org/10.4049/jimmunol.1201989"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23315072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23315072"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Jing Wang, Jes S Lindholt, Galina K Sukhova, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The coreceptor CD4 is expressed in distinct nanoclusters and does not colocalize with T-cell receptor and active protein tyrosine kinase p56lck."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1503532112"}], "href": "https://doi.org/10.1073/pnas.1503532112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25829544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25829544"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "MacLean Sellars, Jun R Huh, Kenneth Day, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3198"}], "href": "https://doi.org/10.1038/ni.3198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26030024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26030024"}]}, {"type": "r", "ref": 49, "children": [{"type": "t", "text": "Lucile Garidou, Céline Pomié, Pascale Klopp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2015.06.001"}], "href": "https://doi.org/10.1016/j.cmet.2015.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26154056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26154056"}]}]}]}