Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes
Open Access
- 5 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-16
- https://doi.org/10.1038/s41598-020-76109-y
Abstract
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.Funding Information
- Department of Biotechnology, Ministry of Science and Technology, India (BT/PR13378/MED/30/1530/2015)
This publication has 43 references indexed in Scilit:
- The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell HomeostasisScience, 2013
- GPR15-Mediated Homing Controls Immune Homeostasis in the Large Intestine MucosaScience, 2013
- Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 DiabetesPLOS ONE, 2011
- Defective Differentiation of Regulatory FoxP3+ T Cells by Small-Intestinal Dendritic Cells in Patients With Type 1 DiabetesDiabetes, 2011
- Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA TrialPLOS ONE, 2011
- Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acidThe Journal of Experimental Medicine, 2007
- The CXCR4/CXCL12 (SDF-1) signalling pathway protects non-obese diabetic mouse from autoimmune diabetesClinical and Experimental Immunology, 2007
- Islet β-Cell-Specific T Cells Can Use Different Homing Mechanisms to Infiltrate and Destroy Pancreatic IsletsThe American Journal of Pathology, 2007
- MAdCAM‐1 is needed for diabetes development mediated by the T cell clone, BDC‐2·5Immunology, 2005
- Diabetogenic T cells are primed both in pancreatic and gut‐associated lymph nodes in NOD miceEuropean Journal of Immunology, 2003