{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM176B, a member of the MS4A family of transmembrane proteins, functions as a putative ion channel whose dysregulation is associated with cancer and altered immune responses. Initial studies revealed that TMEM176B expression is elevated in certain neoplastic tissues such as lymphomas and, when evaluated together with its homologue TMEM176A, may serve as a diagnostic or prognostic marker in cancers including lung and breast carcinomas. These findings underscore its potential role in modulating tumor biology, possibly through direct protein–protein interactions with TMEM176A."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations in immune subsets have demonstrated that TMEM176B is strongly expressed in RORγt(+) cells such as T helper 17 cells, group 3 innate lymphoid cells, and IL-17-producing γδ T cells. Functionally, TMEM176B exhibits cation channel activity, with localization near the trans-Golgi network, suggesting a role in post-Golgi trafficking that influences type 17 immunity. Notably, deficiency of TMEM176B in mouse models leads to decreased psoriasis-like skin inflammation, thereby linking its channel activity to the modulation of inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in adaptive immunity, TMEM176B is overexpressed in immune cells following chronic central nervous system injuries such as spinal cord injury. The concomitant upregulation of TMEM176B (and TMEM176A) in circulating monocytes and the known inhibitory effect on dendritic cell maturation suggest that this protein complex may contribute to the suppression of neuroprotective immune responses, highlighting a novel target for immune-based therapies aimed at restoring protective autoimmunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, TMEM176B has been identified as a negative regulator of the Nlrp3 inflammasome in murine models, where its inhibition leads to enhanced anti-tumoral responses, a finding of potential importance in colorectal cancer prognosis. This anti-inflammatory dimension further complements its role in cancer cell proliferation and migration, as evidenced in breast cancer studies implicating TMEM176B in the activation of key signaling pathways such as AKT/mTOR. Collectively, these observations position TMEM176B as an important mediator at the intersection of cancer progression and immune regulation, making it a promising candidate for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Math P Cuajungco, William Podevin, Vinod K Valluri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Histochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.acthis.2011.12.006"}], "href": "https://doi.org/10.1016/j.acthis.2011.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22244448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22244448"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chifei Kang, Ran Rostoker, Sarit Ben-Shumel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM176B Regulates AKT/mTOR Signaling and Tumor Growth in Triple-Negative Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells10123430"}], "href": "https://doi.org/10.3390/cells10123430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34943938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34943938"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lucile Drujont, Aurélie Lemoine, Aurélie Moreau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep23682"}], "href": "https://doi.org/10.1038/srep23682"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27009467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27009467"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gabriela Picotto, Leslie R Morse, Nguyen Nguyen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM176A and TMEM176B Are Candidate Regulators of Inhibition of Dendritic Cell Maturation and Function after Chronic Spinal Cord Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurotrauma (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/neu.2019.6498"}], "href": "https://doi.org/10.1089/neu.2019.6498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31354034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31354034"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Raylane Adrielle Gonçalves Cambui, Fernanda Pereira Fernandes, Vinicius Nunes Cordeiro Leal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Ala134Thr variant in TMEM176B exerts a beneficial role in colorectal cancer prognosis by increasing NLRP3 inflammasome activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-022-04284-8"}], "href": "https://doi.org/10.1007/s00432-022-04284-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35980484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35980484"}]}]}]}