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Regulatory T Cell-Derived TGF-ß1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity.
Turner, Jacob A; Stephen-Victor, Emmanuel; Wang, Sen; Rivas, Magali Noval; Abdel-Gadir, Azza; Harb, Hani; Cui, Ye; Fanny, Manoussa; Charbonnier, Louis-Marie; Fong, Jason Jun Hung; Benamar, Mehdi; Wang, Leighanne; Burton, Oliver T; Bansal, Kushagra; Bry, Lynn; Zhu, Chengsong; Li, Quan-Zhen; Clement, Rachel L; Oettgen, Hans C; Crestani, Elena; Rachid, Rima; Sage, Peter T; Chatila, Talal A.
Afiliação
  • Turner JA; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Stephen-Victor E; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Wang S; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Rivas MN; Division of Pediatric Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC), Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Abdel-Gadir A; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Harb H; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Cui Y; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Fanny M; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Charbonnier LM; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Fong JJH; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Benamar M; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Wang L; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Burton OT; Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridgeshire CB22 3AT, UK.
  • Bansal K; Molecular Biology & Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
  • Bry L; Massachusetts Host-Microbiome Center, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Zhu C; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Li QZ; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Clement RL; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Oettgen HC; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Crestani E; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Rachid R; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Sage PT; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Chatila TA; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: talal.chatila@childrens.harvard.edu.
Immunity ; 53(6): 1202-1214.e6, 2020 12 15.
Article em En | MEDLINE | ID: mdl-33086036
ABSTRACT
The mechanisms by which regulatory T (Treg) cells differentially control allergic and autoimmune responses remain unclear. We show that Treg cells in food allergy (FA) had decreased expression of transforming growth factor beta 1 (TGF-ß1) because of interleukin-4 (IL-4)- and signal transducer and activator of transciription-6 (STAT6)-dependent inhibition of Tgfb1 transcription. These changes were modeled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependent retinoic acid receptor-related orphan receptor gamma t (ROR-γt)+ Treg cell differentiation. This dysregulation was rescued by treatment with Clostridiales species, which upregulated Tgfb1 expression in Treg cells. Biallelic deficiency precipitated fatal autoimmunity with intense autoantibody production and dysregulated T follicular helper and B cell responses. These results identify a privileged role of Treg cell-derived TGF-ß1 in regulating allergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose- and microbiota-dependent manner.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoimunidade / Linfócitos T Reguladores / Fator de Crescimento Transformador beta1 / Hipersensibilidade Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Animals / Child / Child, preschool / Humans / Infant Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoimunidade / Linfócitos T Reguladores / Fator de Crescimento Transformador beta1 / Hipersensibilidade Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Animals / Child / Child, preschool / Humans / Infant Idioma: En Ano de publicação: 2020 Tipo de documento: Article