{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent investigations have revealed that Tmem106a, a type II transmembrane protein highly expressed on macrophages, plays a critical role in modulating their activation and polarization. One study demonstrated that triggering Tmem106a using a specific antibody upregulates key surface markers—including CD80, CD86, CD69, and MHC II—and induces the release of pro‐inflammatory mediators such as TNF‑α, IL‑1β, IL‑6, CCL2, and nitric oxide. This antibody-induced activation promoted increased iNOS production and STAT1 phosphorylation while also triggering MAPK (ERK-1/2, JNK, p38) and NF‑κB signaling, ultimately driving macrophages toward an M1-like inflammatory phenotype—a response that was significantly diminished upon siRNA-mediated Tmem106a knockdown."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nIn a complementary study, macrophages exhibited increased Tmem106a expression upon lipopolysaccharide (LPS) stimulation, a finding that extended to peripheral monocytes from septic patients. Notably, Tmem106a-deficient mice were markedly more susceptible to LPS-induced septic shock. The absence of Tmem106a in macrophages led to enhanced expression of activation markers (CD80, CD86, and MHC II) and an upregulation of pro-inflammatory mediators including TNF‑α, IL‑6, IFN‑β, and iNOS, with these effects being linked to augmented MAPK and NF‑κB signaling. Collectively, these data underscore the regulatory role of Tmem106a in restraining excessive M1 polarization and maintaining macrophage homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hui Dai, Dong Xu, Jing Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transmembrane protein 106a activates mouse peritoneal macrophages via the MAPK and NF-κB signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep12461"}], "href": "https://doi.org/10.1038/srep12461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26215746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26215746"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "X Zhang, T Feng, X Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inactivation of TMEM106A promotes lipopolysaccharide-induced inflammation via the MAPK and NF-κB signaling pathways in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cei.13528"}], "href": "https://doi.org/10.1111/cei.13528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33006758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33006758"}]}]}]}