{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:32:00Z","timestamp":1788517920360,"version":"build-2803163510"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Toll\/interleukin-1 receptor domain-containing adaptor protein (TIRAP) is a key adaptor in Toll-like receptor signaling, classically functioning as a cytoplasmic bridging adaptor for Myeloid differentiation primary response 88 (MyD88) recruitment. While its role in inflammatory signaling is well established, its contribution to alcohol-induced liver fibrosis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used lipopolysaccharide (LPS) and ethanol-stimulated hepatic stellate cells (LX-2) for\n                      <jats:italic>in vitro<\/jats:italic>\n                      analysis. Immunofluorescence and immunoblotting were performed to check TIRAP\u2019s expression. siRNA was used for TIRAP silencing to monitor its significant activity. mRNA expression for pro-fibrotic markers was checked via qRT-PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrated for the first time, nuclear translocation of TIRAP under alcoholic conditions. Confocal microscopy and nuclear\u2013cytoplasmic fractionation confirmed TIRAP enrichment in the nucleus. Importantly, silencing of TIRAP in LX-2 significantly reduced the nuclear translocation and expression of fibrotic markers (such as\n                      <jats:italic>\u03b1-SMA<\/jats:italic>\n                      and\n                      <jats:italic>collagen<\/jats:italic>\n                      ) in HSCs, suggesting a key role of nuclear TIRAP in driving fibrogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, these findings reveal a novel role for TIRAP beyond cytoplasmic signaling, suggesting potential nuclear functions that may regulate transcriptional programs driving inflammation and fibrosis.<\/jats:p>\n                  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