{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:56:11Z","timestamp":1787756171614,"version":"build-2784847793"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009988","name":"Huzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009988","id-type":"DOI","asserted-by":"publisher"}]}],"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>T cell receptor-associated transmembrane adaptor 1 (TRAT1) is a well-characterized regulator of T-cell signaling, yet its functional roles in innate lymphocytes remain largely undefined. This study aimed to identify autoimmune hepatitis (AIH)-associated immune targets and perform an exploratory functional characterization of TRAT1 in NK-cell models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed transcriptomic analysis on liver tissues from AIH patients and disease controls to prioritize candidate genes. Public datasets and a Concanavalin A (ConA)-induced acute immune-mediated hepatitis murine model were used for contextualization and experimental support for Trat1 expression and immune cell dynamics. The functional role of TRAT1 in NK cells was assessed using NK92-MI cells and primary human NK cells with siRNA-mediated TRAT1 knockdown (KD). TRAT1 expression kinetics and cytotoxicity were examined in both systems, whereas proliferation, effector molecule production, surface receptor expression, calcium flux, and mitogen-activated protein kinase (MAPK) signaling were further analyzed in NK92-MI cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TRAT1 was prioritized as an AIH-enriched immune-related candidate gene in this discovery cohort. In the ConA-induced acute immune-mediated hepatitis model,\n                      <jats:italic>Trat1<\/jats:italic>\n                      expression was selectively elevated in sorted hepatic NK-cell-enriched populations.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , TRAT1 mRNA expression transiently increased in both NK92-MI and primary human NK cells upon activation; its knockdown subsequently enhanced their cytotoxicity against target cells. In NK92-MI cells, TRAT1 deficiency led to enhanced proliferation and elevated production of Interferon-gamma (IFN-\u03b3), Tumor necrosis factor-alpha (TNF-\u03b1), Granzyme B (GZMB), and perforin. TRAT1 deficiency also selectively upregulated activating receptors NCR1 (NKp46) and NCR2 (NKp44) while downregulating NKG2D. Mechanistically, TRAT1 KD was associated with increased Ca\u00b2\n                      <jats:sup>+<\/jats:sup>\n                      influx, phospholipase C gamma 2 (PLC\u03b32) phosphorylation, and the phosphorylation of ERK1\/2 and p38.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Through an exploratory transcriptomic discovery approach, this study suggests that TRAT1 acts as an\n                      <jats:italic>in vitro<\/jats:italic>\n                      candidate negative modulator of NK-cell effector functions, potentially involving calcium and MAPK signaling in NK92-MI cells. These data support TRAT1 as a candidate mechanistic lead for future validation in larger clinical cohorts and lineage-specific\n                      <jats:italic>in vivo<\/jats:italic>\n                      models.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1843865","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:45:35Z","timestamp":1783403135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic profiling of autoimmune hepatitis identifies TRAT1 as an in vitro negative regulator of NK cell effector functions"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiapeng","family":"Gao","sequence":"first","affiliation":[{"name":"First Affiliated Hospital, Huzhou Normal University","place":["Huzhou, China"]},{"name":"School of Medicine & Nursing, Huzhou Normal University","place":["Huzhou, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine & Nursing, Huzhou Normal University","place":["Huzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Medicine & Nursing, Huzhou Normal University","place":["Huzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanzi","family":"Hong","sequence":"additional","affiliation":[{"name":"School of Medicine & Nursing, Huzhou Normal University","place":["Huzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunliang","family":"Yao","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital, Huzhou Normal University","place":["Huzhou, China"]},{"name":"School of Medicine & Nursing, Huzhou Normal University","place":["Huzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Feng","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital, Huzhou Normal University","place":["Huzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"18017","DOI":"10.1002\/9780470691861.ch11b","article-title":"Autoimmune hepatitis","volume":"4","author":"Mieli-Vergani","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B2","first-page":"869","article-title":"Autoimmune hepatitis","volume-title":"Translational Hepatology: Molecular, Clinical and Therapeutic Aspects","author":"Beretta-Piccoli","year":"2024"},{"key":"B3","doi-asserted-by":"publisher","first-page":"13578","DOI":"10.3390\/ijms222413578","article-title":"Pathogenesis of autoimmune hepatitis-cellular and molecular 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