title: Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes.
creator: Jacob, Neenu
creator: Jaiswal, Shivani
creator: Maheshwari, Deep
creator: Nallabelli, Nayudu
creator: Khatri, Neeraj
creator: Bhatia, Alka
creator: Bal, Amanjit
creator: Malik, Vivek
creator: Verma, Savita
creator: Kumar, Rakesh
creator: Sachdeva,  Naresh
subject: QR Microbiology
description: Type-1 diabetes (T1D) is an autoimmune disease caused by progressive loss of insulin-producing beta cells in the pancreas. Butyrate is a commensal microbial-derived metabolite, implicated in intestinal homeostasis and immune regulation. Here, we investigated the mechanism of diabetes remission in non-obese diabetic (NOD) mice following butyrate administration. Sodium butyrate (150 mM) was administered to female NOD mice in drinking water after the onset of hyperglycemia (15-25 weeks age) and at 4 weeks of age (early-intervention group). Butyrate administration reduced the progression of hyperglycemia in diabetic mice and delayed onset of diabetes in the early-intervention group with a reduction in insulitis. Butyrate administration increased regulatory T cells (Tregs) in the colon, mesenteric lymph nodes, Peyer's patches, and its protective effects diminished upon depletion of Tregs. Further, an increase in alpha 4 beta 7, CCR9, and GPR15 expressing Tregs in the pancreatic lymph nodes (PLN) and pancreas in butyrate-treated mice suggested migration of gut-primed Tregs towards the pancreas. Finally, the adoptive transfer experiments demonstrated that induced Tregs from gut-associated lymphoid tissue can migrate towards the pancreas and PLN and delay the onset of diabetes. Our results thus suggest that early administration of butyrate can restore immunological tolerance during T1D via induction of Tregs with migratory capabilities.
publisher: Nature publishing group
date: 2020-11-05
type: Article
type: PeerReviewed
identifier:   Jacob, Neenu and Jaiswal, Shivani and Maheshwari, Deep and Nallabelli, Nayudu and Khatri, Neeraj and Bhatia, Alka and Bal, Amanjit and Malik, Vivek and Verma, Savita and Kumar, Rakesh and Sachdeva, Naresh  (2020) Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes.  Scientific reports, 10 (1).   ISSN 2045-2322     
relation: http://crdd.osdd.net/open/2619/