Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines
Year: 2020
Type: preprint
Abstract: 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 + T regs in the small intestine inversely correlated with the response to oral vaccination. Depletion of RORγT + FOXP3 + T regs indicated that they were necessary for EED-associated inhibition of the vaccine response. Additionally, RORγT + FOXP3 + T regs 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.
Institutions: University of Pittsburgh, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Central South University, National Institutes of Health, Genentech, National Institute of Allergy and Infectious Diseases, Stanford Medicine, Stanford University, Arsenal Biosciences (United States), Benaroya Research Institute, Universidade de São Paulo, Tulane University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Damon Runyon Cancer Research Foundation, University of Pittsburgh, China University of Mining and Technology, National Institutes of Health, Center for Research Computing, University of Pittsburgh, National Institute of Allergy and Infectious Diseases, Children's Hospital of Pittsburgh, NHLBI Division of Intramural Research
OpenAlex ID: W3033568660