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Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling.
Pawlak, Mathias; DeTomaso, David; Schnell, Alexandra; Meyer Zu Horste, Gerd; Lee, Youjin; Nyman, Jackson; Dionne, Danielle; Regan, Brianna M L; Singh, Vasundhara; Delorey, Toni; Schramm, Markus A; Wang, Chao; Wallrapp, Antonia; Burkett, Patrick R; Riesenfeld, Samantha J; Anderson, Ana C; Regev, Aviv; Xavier, Ramnik J; Yosef, Nir; Kuchroo, Vijay K.
Afiliação
  • Pawlak M; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • DeTomaso D; Department of Electrical Engineering and Computer Sciences and Center for Computational Biology, UC Berkeley, Berkeley, CA 94720, USA.
  • Schnell A; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Meyer Zu Horste G; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Lee Y; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Nyman J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Dionne D; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Regan BML; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Singh V; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Delorey T; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Schramm MA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Wang C; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wallrapp A; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Burkett PR; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Riesenfeld SJ; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Anderson AC; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Xavier RJ; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, MGH, Boston, MA 02114, USA. Electronic address: rxavier@broadinstitute.org.
  • Yosef N; Department of Electrical Engineering and Computer Sciences and Center for Computational Biology, UC Berkeley, Berkeley, CA 94720, USA; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic addr
  • Kuchroo VK; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: vkuchroo@rics.bwh.harvard.edu.
Immunity ; 55(9): 1663-1679.e6, 2022 09 13.
Article em En | MEDLINE | ID: mdl-36070768
ABSTRACT
Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Interleucina / Colite Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Interleucina / Colite Idioma: En Ano de publicação: 2022 Tipo de documento: Article