Nuclear receptor coregulator NRIP1 R448G modulates T cell gut homing to control intestinal inflammation

• 成果类型: Article
• 署名作者: Chen, Xiangjun; Hwang, Hee Seung; Li, Bihua; Zhao, Yanhua; Ghosh, Koushik; Deng, Lei; Creasey, Elizabeth A.; Ashenberg, Orr; Graham, Daniel B.; Xavier, Ramnik J.
• 署名单位: Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Brigham & Women's Hospital; Harvard University; Harvard Medical School
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10519
• DOI: 10.1073/pnas.2508269122
• 发表日期: 2025-09-23
• 关键词: scale single-cell; retinoic acid; rip140; expression; metabolism; macrophage; induction; responses; colitis; loci

摘要

Nuclear receptors (NRs) are crucial to integrate metabolite sensing and immune responses in the gut. NR- interacting protein 1 (NRIP1) is an important coregulator of various NRs that has been implicated in inflammatory bowel disease risk, but mechanistic details of how NRIP1 controls NR activities mediating immune homeostasis and inflammation remain elusive. We demonstrate that a missense risk tory cytokine production, ultimately leading to exacerbated intestinal inflammation. Mechanistically, NRIP1 acts as a corepressor in retinoic acid signaling by expression of a gut- homing transcriptional program. Our study reveals the impacts of NRIP1 on CD4+ T cells in immune regulation during intestinal inflammation, providing and tissue inflammation.