دورية أكاديمية
أعرض في EDS

T Follicular Regulatory Cell-Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity.

التفاصيل البيبلوغرافية
العنوان: T Follicular Regulatory Cell-Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity.
المؤلفون: 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.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115., Sharpe AH; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115., Sobel RA; Department of Pathology, Stanford University, Stanford, CA 94305; and., Quintana FJ; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115., Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142., Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142., Wang C; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Yosef N; Department of Electrical Engineering and Computer Science, Center for Computational Biology, University of California, Berkeley, CA 94720., Kuchroo VK; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; vkuchroo@evergrande.hms.harvard.edu.; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142.; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.
المصدر: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 Dec 15; Vol. 205 (12), pp. 3247-3262. Date of Electronic Publication: 2020 Nov 09.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-
مواضيع طبية MeSH: Antibody Formation*, Autoantibodies/*immunology , Autoimmune Diseases/*immunology , B-Lymphocytes/*immunology , Fibrinogen/*immunology, Animals ; Antigens, CD/genetics ; Antigens, CD/immunology ; Autoimmune Diseases/genetics ; Fibrinogen/genetics ; Hepatitis A Virus Cellular Receptor 2/genetics ; Hepatitis A Virus Cellular Receptor 2/immunology ; Mice ; Mice, Knockout ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology ; T-Lymphocytes, Regulatory/immunology ; Lymphocyte Activation Gene 3 Protein
مستخلص: 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.
(Copyright © 2020 by The American Association of Immunologists, Inc.)
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معلومات مُعتمدة: P01 AI039671 United States AI NIAID NIH HHS; P01 AI056299 United States AI NIAID NIH HHS; P01 AI073748 United States AI NIAID NIH HHS; P01 AI129880 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Antigens, CD)
0 (Autoantibodies)
0 (Fgl2 protein, mouse)
0 (Havcr2 protein, mouse)
0 (Hepatitis A Virus Cellular Receptor 2)
0 (Pdcd1 protein, mouse)
0 (Programmed Cell Death 1 Receptor)
0 (Receptors, Immunologic)
0 (T cell Ig and ITIM domain protein, mouse)
9001-32-5 (Fibrinogen)
0 (Lymphocyte Activation Gene 3 Protein)
0 (Lag3 protein, mouse)
تواريخ الأحداث: Date Created: 20201110 Date Completed: 20210413 Latest Revision: 20221207
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7725915
DOI: 10.4049/jimmunol.2000748
PMID: 33168576
قاعدة البيانات: MEDLINE
الوصف
تدمد:1550-6606
DOI:10.4049/jimmunol.2000748