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Abstract
Environmental enteric dysfunction (EED) is a gastrointestinal inflammatory disease caused by malnutrition and chronic infection. EED is associated with stunting in children and reduced efficacy of oral vaccines. To study the mechanisms of oral vaccine failure during EED, we developed a microbiota- and diet-dependent mouse EED model. Analysis of E. coli-labile toxin vaccine-specific CD4+ T cells in these mice revealed impaired CD4+ T cell responses in the small intestine and but not the lymph nodes. EED mice exhibited increased frequencies of small intestine-resident ROR?T+FOXP3+ regulatory T (Treg) cells. Targeted deletion of ROR?T from Treg cells restored small intestinal vaccine-specific CD4 T cell responses and vaccine-mediated protection upon challenge. However, ablation of ROR?T+FOXP3+ Treg cells made mice more susceptible to EED-induced stunting. Our findings provide insight into the poor efficacy of oral vaccines in EED and highlight how ROR?T+FOXP3+ Treg cells can regulate intestinal immunity while leaving systemic responses intact.
View details for DOI 10.1016/j.immuni.2021.07.005
View details for Web of Science ID 000684589700013
View details for PubMedID 34348118