{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIRAK‑M (also known as IL‑1 receptor‑associated kinase‑M) is an inducible, catalytically inactive regulator that is expressed predominantly in myeloid cells and functions as a critical negative checkpoint of Toll‑like receptor (TLR) and IL‑1 receptor signaling. Upon TLR stimulation by microbial products or other endogenous ligands, IRAK‑M is upregulated and disrupts the assembly and dissociation of signaling complexes (including the MyD88‑IRAK‑1/‑4‑TRAF6 complex), thereby attenuating downstream MAP kinase and NF‑κB activation. This negative feedback mechanism is essential not only for limiting pro‑inflammatory cytokine production and preventing excessive tissue damage—as seen in endotoxin tolerance and during bacterial or viral infections—but also to maintain innate immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in innate immunity, IRAK‑M influences the activation state and polarization of various immune cell types—including macrophages, dendritic cells, microglia, and neutrophils—thereby modulating both local and systemic inflammatory as well as adaptive responses. Its activity shapes the outcomes of diverse pathological conditions such as sepsis, lung and liver injury, autoimmune diseases, fibrosis, osteoclast‐mediated bone loss, and even tumor progression by regulating cytokine profiles, chemokine production, and cell survival. This pleiotropic function of IRAK‑M is further orchestrated through cross‑talk with other signaling pathways (including MAPKs, PI3K/Akt, and STATs), underscoring its central role in balancing protective immunity with the risk for immune‑mediated pathology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, recent studies have unraveled additional layers of IRAK‑M regulation that have implications for the modulation of both innate and adaptive immunity. For instance, IRAK‑M influences the differentiation and function of regulatory T cells and impacts immune checkpoint responses, thereby affecting resistance to infections and the efficacy of immunotherapies. It also plays a role in gastrointestinal immune tolerance, bone marrow reconstitution, and the fine‑tuning of inflammatory responses in the central nervous system and other tissues—revealing IRAK‑M as a promising therapeutic target to recalibrate immune responses in a variety of chronic inflammatory and neoplastic diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Koichi Kobayashi, Lorraine D Hernandez, Jorge E Galán, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRAK-M is a negative regulator of Toll-like receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)00827-9"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "00827-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12150927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12150927"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kuniko Nakayama, Shu Okugawa, Shintaro Yanagimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of IRAK-M in peptidoglycan-induced tolerance in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308620200"}], "href": "https://doi.org/10.1074/jbc.M308620200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14660668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14660668"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hongmei Li, Esteban Cuartas, Weiguo Cui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-1 receptor-associated kinase M is a central regulator of osteoclast differentiation and activation."}]}, {"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.20041444"}], "href": "https://doi.org/10.1084/jem.20041444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15809356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15809356"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sushil Kumar Pathak, Sanchita Basu, Asima Bhattacharyya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mycobacterium tuberculosis lipoarabinomannan-mediated IRAK-M induction negatively regulates Toll-like receptor-dependent interleukin-12 p40 production in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506471200"}], "href": "https://doi.org/10.1074/jbc.M506471200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16263713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16263713"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jianmin Su, Qifa Xie, Ingred Wilson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2007.02.009"}], "href": "https://doi.org/10.1016/j.cellsig.2007.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17379480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17379480"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Koichi Takebayashi, Ryota Hokari, Chie Kurihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oral tolerance induced by enterobacteria altered the process of lymphocyte recruitment to intestinal microvessels: roles of endothelial cell adhesion molecules, TGF-beta and negative regulators of TLR signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microcirculation (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/10739680802574166"}], "href": "https://doi.org/10.1080/10739680802574166"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19225984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19225984"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ferdaus Hassan, Shamima Islam, Gantsetseg Tumurkhuu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of interleukin-1 receptor-associated kinase (IRAK)-M in toll-like receptor (TLR) 7-mediated tolerance in RAW 264.7 macrophage-like cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellimm.2009.01.013"}], "href": "https://doi.org/10.1016/j.cellimm.2009.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19251253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19251253"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Vassiliki Zacharioudaki, Ariadne Androulidaki, Alicia Arranz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adiponectin promotes endotoxin tolerance in macrophages by inducing IRAK-M expression."}]}, {"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.0803694"}], "href": "https://doi.org/10.4049/jimmunol.0803694"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19414798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19414798"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Heimo Lagler, Omar Sharif, Isabella Haslinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TREM-1 activation alters the dynamics of pulmonary IRAK-M expression in vivo and improves host defense during pneumococcal pneumonia."}]}, {"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.0803862"}], "href": "https://doi.org/10.4049/jimmunol.0803862"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19596984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19596984"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jianmin Su, Tongli Zhang, John Tyson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The interleukin-1 receptor-associated kinase M selectively inhibits the alternative, instead of the classical NFkappaB pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Innate Immun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000158541"}], "href": "https://doi.org/10.1159/000158541"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19809574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19809574"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Masafumi Seki, Shigeru Kohno, Michael W Newstead, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of IL-1 receptor-associated kinase-M in regulating chemokine-dependent deleterious inflammation in murine influenza pneumonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0901709"}], "href": "https://doi.org/10.4049/jimmunol.0901709"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20042589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20042589"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Leah L N Hubbard, Megan N Ballinger, Peedikayil E Thomas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for IL-1 receptor-associated kinase-M in prostaglandin E2-induced immunosuppression post-bone marrow transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0902828"}], "href": "https://doi.org/10.4049/jimmunol.0902828"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20439918"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20439918"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Kenneth Lyn-Kew, Eric Rich, Xianying Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0011145"}], "href": "https://doi.org/10.1371/journal.pone.0011145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20585389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20585389"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Martin Berglund, Silvia Melgar, Koichi S Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-1 receptor-associated kinase M downregulates DSS-induced colitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Bowel Dis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ibd.21287"}], "href": "https://doi.org/10.1002/ibd.21287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20848470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20848470"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Hiroshi Kobayashi, Anna Nolan, Bushra Naveed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neutrophils activate alveolar macrophages by producing caspase-6-mediated cleavage of IL-1 receptor-associated kinase-M."}]}, {"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.1001906"}], "href": "https://doi.org/10.4049/jimmunol.1001906"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21098228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21098228"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Tina L Sumpter, Vignesh Packiam, Heth R Turnquist, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DAP12 promotes IRAK-M expression and IL-10 production by liver myeloid dendritic cells and restrains their T cell allostimulatory ability."}]}, {"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.1000527"}], "href": "https://doi.org/10.4049/jimmunol.1000527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21257958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21257958"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Yanbao Xiong, Andrei E Medvedev "}, {"type": "b", "children": [{"type": "t", "text": "Induction of endotoxin tolerance in vivo inhibits activation of IRAK4 and increases negative regulators IRAK-M, SHIP-1, and A20."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.0611273"}], "href": "https://doi.org/10.1189/jlb.0611273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21934070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21934070"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Tyler S Cole, Min Zhang, Theodore J Standiford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II after bacterial re-stimulation of tolerized dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunol Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.imlet.2012.03.006"}], "href": "https://doi.org/10.1016/j.imlet.2012.03.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22472665"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22472665"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yangchun Zhang, Shiming Yu, Jianhong Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wear particles promote endotoxin tolerance in macrophages by inducing interleukin-1 receptor-associated kinase-M expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biomed Mater Res A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbm.a.34375"}], "href": "https://doi.org/10.1002/jbm.a.34375"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22941946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22941946"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Hao Zhou, Minjia Yu, Koichi Fukuda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRAK-M mediates Toll-like receptor/IL-1R-induced NFκB activation and cytokine production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2013.2"}], "href": "https://doi.org/10.1038/emboj.2013.2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23376919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23376919"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Klara Klimesova, Miloslav Kverka, Zuzana Zakostelska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered gut microbiota promotes colitis-associated cancer in IL-1 receptor-associated kinase M-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Bowel Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MIB.0b013e318281330a"}], "href": "https://doi.org/10.1097/MIB.0b013e318281330a"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23567778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23567778"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Nak-Yun Sung, Mi-So Yang, Du-Sub Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.07.038"}], "href": "https://doi.org/10.1016/j.bbrc.2013.07.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23872113"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23872113"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "M Jeyanathan, S McCormick, R Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pulmonary M. tuberculosis infection delays Th1 immunity via immunoadaptor DAP12-regulated IRAK-M and IL-10 expression in antigen-presenting cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mucosal Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mi.2013.86"}], "href": "https://doi.org/10.1038/mi.2013.86"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24172845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24172845"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Megan N Ballinger, Michael W Newstead, Xianying Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRAK-M promotes alternative macrophage activation and fibroproliferation in bleomycin-induced lung injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1402377"}], "href": "https://doi.org/10.4049/jimmunol.1402377"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25595781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25595781"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Rebecca Kesselring, Joachim Glaesner, Andreas Hiergeist, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2016.03.014"}], "href": "https://doi.org/10.1016/j.ccell.2016.03.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27150039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27150039"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Konstantina Lyroni, Andreas Patsalos, Maria G Daskalaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic and Transcriptional Regulation of IRAK-M Expression in Macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1600009"}], "href": "https://doi.org/10.4049/jimmunol.1600009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28011933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28011933"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Stefanie Steiger, Santhosh V Kumar, Mohsen Honarpisheh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1601982"}], "href": "https://doi.org/10.4049/jimmunol.1601982"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28701510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28701510"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Morris Nechama, Jeahoo Kwon, Shuo Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03886-6"}], "href": "https://doi.org/10.1038/s41467-018-03886-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29686383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29686383"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Yi-An Ko, Yueh-Hsuan Chan, Chin-Hsiu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blimp-1-Mediated Pathway Promotes Type I IFN Production in Plasmacytoid Dendritic Cells by Targeting to Interleukin-1 Receptor-Associated Kinase M."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2018.01828"}], "href": "https://doi.org/10.3389/fimmu.2018.01828"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30131810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30131810"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Cun-Jin Zhang, Meiling Jiang, Hao Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR-stimulated IRAKM activates caspase-8 inflammasome in microglia and promotes neuroinflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI121901"}], "href": "https://doi.org/10.1172/JCI121901"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30372424"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30372424"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Yao Zhang, Na Diao, Christina K Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neutrophils Deficient in Innate Suppressor IRAK-M Enhances Anti-tumor Immune Responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2019.09.019"}], "href": "https://doi.org/10.1016/j.ymthe.2019.09.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31607540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31607540"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Kisha Pradhan, Shuo Geng, Yao Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRAM-Related TLR4 Pathway Antagonized by IRAK-M Mediates the Expression of Adhesion/Coactivating Molecules on Low-Grade Inflammatory Monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.2000978"}], "href": "https://doi.org/10.4049/jimmunol.2000978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34031144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34031144"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Gürcan Tunalı, Marta Rúbies Bedós, Divya Nagarajan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-1 receptor-associated kinase-3 acts as an immune checkpoint in myeloid cells to limit cancer immunotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI161084"}], "href": "https://doi.org/10.1172/JCI161084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36757800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36757800"}]}]}]}