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T Follicular Regulatory Cell-Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity.
Sungnak, Waradon; Wagner, Allon; Kowalczyk, Monika S; Bod, Lloyd; Kye, Yoon-Chul; Sage, Peter T; Sharpe, Arlene H; Sobel, Raymond A; Quintana, Francisco J; Rozenblatt-Rosen, Orit; Regev, Aviv; Wang, Chao; Yosef, Nir; Kuchroo, Vijay K.
Afiliação
  • Sungnak W; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
  • Wagner A; Department of Electrical Engineering and Computer Science, Center for Computational Biology, University of California, Berkeley, CA 94720.
  • Kowalczyk MS; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Bod L; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
  • Kye YC; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
  • Sage PT; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
  • Sharpe AH; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
  • Sobel RA; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
  • Quintana FJ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
  • Rozenblatt-Rosen O; Department of Pathology, Stanford University, Stanford, CA 94305; and.
  • Regev A; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.
  • Wang C; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Yosef N; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Kuchroo VK; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
J Immunol ; 205(12): 3247-3262, 2020 12 15.
Article em En | MEDLINE | ID: mdl-33168576
T follicular regulatory (TFR) cells limit Ab responses, but the underlying mechanisms remain largely unknown. In this study, we identify Fgl2 as a soluble TFR cell effector molecule through single-cell gene expression profiling. Highly expressed by TFR cells, Fgl2 directly binds to B cells, especially light-zone germinal center B cells, as well as to T follicular helper (TFH) cells, and directly regulates B cells and TFH in a context-dependent and type 2 Ab isotype-specific manner. In TFH cells, Fgl2 induces the expression of Prdm1 and a panel of checkpoint molecules, including PD1, TIM3, LAG3, and TIGIT, resulting in TFH cell dysfunction. Mice deficient in Fgl2 had dysregulated Ab responses at steady-state and upon immunization. In addition, loss of Fgl2 results in expansion of autoreactive B cells upon immunization. Consistent with this observation, aged Fgl2-/- mice spontaneously developed autoimmunity associated with elevated autoantibodies. Thus, Fgl2 is a TFR cell effector molecule that regulates humoral immunity and limits systemic autoimmunity.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Doenças Autoimunes / Fibrinogênio / Linfócitos B / Formação de Anticorpos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Doenças Autoimunes / Fibrinogênio / Linfócitos B / Formação de Anticorpos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article