IL-15 promotes inflammatory T h 17 cells in the intestine
IL-15 promotes inflammatory T h 17 cells in the intestine
ABSTRACT Ulcerative Colitis (UC) is a chronic gastrointestinal condition with high morbidity. While modern medical therapies have revolutionized the care of UC, 10-25% of patients fail medications and still progress to surgery. Thus, developing new treatments is a core problem in UC. T-cells, especially Th17 cells, are strongly linked with UC and are major targets of medications in UC. Tissue-resident memory T-cells (TRM) are a distinct class of T-cells that are highly enriched in the intestine, closely aligned with the microbiota, and are implicated in the pathogenesis of UC. Unlike circulating T-cells, TRM are difficult to target because they do not recirculate. Thus, we focused on cytokines like IL-15 which act as a tissue danger signal and regulate T-cells in situ. We found that the IL15 axis is upregulated in UC and predicts treatment response. IL-15 was redundant for Th17 differentiation but could activate terminally differentiated Th17 cells to promote intestinal inflammation. Finally, in CD4+ TRM from patients with UC, IL-15 upregulated RORC, the master transcription factor for Th17 cells, via a Janus Kinase (JAK)1 pathway. Thus, IL-15 promotes terminally differentiated inflammatory Th17 cells in the intestine raising the possibility that IL-15 may be a target for UC treatments.
Bishu Shrinivas、Lee Allen、Berinstein Elliott M、Fry Christopher、Kao John Y、Berinstein Jeff B.、Grassberger Helmut、Golob Jonathan G.、Kamada Nobuhiko、Hou Guoqing、Nemzek Jean、Khaykin Valerie、Zataari Mohamed El
Division of Gastroenterology, University of MichiganDivision of Gastroenterology, University of MichiganDepartment of Medicine, Trinity HealthUnit of Laboratory Animal Medicine, University of MichiganDivision of Gastroenterology, University of MichiganDivision of Gastroenterology, University of MichiganDivision of Gastroenterology, University of MichiganDivision of Infectious Diseases, University of MichiganDivision of Gastroenterology, University of MichiganDivision of Gastroenterology, University of MichiganUnit of Laboratory Animal Medicine, University of MichiganDivision of Gastroenterology, University of MichiganDivision of Gastroenterology, University of Michigan
基础医学内科学临床医学
Bishu Shrinivas,Lee Allen,Berinstein Elliott M,Fry Christopher,Kao John Y,Berinstein Jeff B.,Grassberger Helmut,Golob Jonathan G.,Kamada Nobuhiko,Hou Guoqing,Nemzek Jean,Khaykin Valerie,Zataari Mohamed El.IL-15 promotes inflammatory T h 17 cells in the intestine[EB/OL].(2025-03-28)[2025-05-09].https://www.biorxiv.org/content/10.1101/2023.03.11.532227.点此复制
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