Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines
Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines
Summary Environmental Enteric Dysfunction (EED) is an intestinal disease caused by malnutrition and infection that leads to malabsorption and stunting. EED is also associated with a reduced efficacy of oral vaccines. We show in a microbiota and diet-dependent model of EED that oral vaccine-specific CD4+ T cell responses fail in the small intestine but responses in the draining lymph node were unaffected. Accordingly, the number of immunosuppressive RORγT+FOXP3+ Tregs in the small intestine inversely correlated with the response to oral vaccination. Depletion of RORγT+FOXP3+ Tregs indicated that they were necessary for EED-associated inhibition of the vaccine response. Additionally, RORγT+FOXP3+ Tregs are important to regulate EED-associated inflammation as their depletion significantly worsened stunting. We have shown that EED-associated intestinal inflammation leads to a localized intestinal blockade of CD4 T cell immunity. These results support a modular model for immunity where tissue responses can be regulated independently of systemic immunity to prevent autoinflammation.
Bhattacharjee Amrita、Linehan Jonathan L.、Burr Ansen H.P.、Hall Jason A.、Norton Elizabeth B.、Yang Deyi、Overacre-Delgoffe Abigail E.、Harrison Oliver J.、Spencer Sean P.、Huckestein Brydie R.、da Fonseca Denise Morais、Tometich Justin T.、Hand Timothy W.、Belkaid Yasmine
R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children?ˉs Hospital of Pittsburgh, University of PittsburghMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health||Genentech IncR.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children?ˉs Hospital of Pittsburgh, University of Pittsburgh||Program in Microbiology and Immunology, University of PittsburghMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health||ArsenalBio IncDepartment of Microbiology and Immunology, Tulane University School of MedicineR.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children?ˉs Hospital of Pittsburgh, University of Pittsburgh||Central South University, Xiangya School of MedicineR.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children?ˉs Hospital of Pittsburgh, University of PittsburghMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health||Benaroya Research InstituteMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health||Department of Microbiology and Immunology, Stanford University School of MedicineProgram in Microbiology and Immunology, University of PittsburghMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health||Department of Immunology, Institute of Biomedical Sciences, University of S?o PauloR.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children?ˉs Hospital of Pittsburgh, University of PittsburghR.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children?ˉs Hospital of Pittsburgh, University of Pittsburgh||Program in Microbiology and Immunology, University of PittsburghMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health
基础医学预防医学生物科学研究方法、生物科学研究技术
Bhattacharjee Amrita,Linehan Jonathan L.,Burr Ansen H.P.,Hall Jason A.,Norton Elizabeth B.,Yang Deyi,Overacre-Delgoffe Abigail E.,Harrison Oliver J.,Spencer Sean P.,Huckestein Brydie R.,da Fonseca Denise Morais,Tometich Justin T.,Hand Timothy W.,Belkaid Yasmine.Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines[EB/OL].(2025-03-28)[2025-09-01].https://www.biorxiv.org/content/10.1101/2020.06.03.130831.点此复制
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