Islet Lymphocytes Maintain a Stable Regulatory Phenotype Under Homeostatic Conditions and Metabolic Stress

Frontiers in Immunology

Immunology

Jessica G. Olivas-Corral¹  Seth F. Yannacone²  Erin D. Lucas³  Jennifer C. Whitesell⁴  Rachel S. Friedman⁴  Robin S. Lindsay⁵  Mary H. Schoenbach⁵ 

[1] Barbara Davis Center for Diabetes, Aurora, CO, United States;Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO, United States;Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO, United States;Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States;Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States;Barbara Davis Center for Diabetes, Aurora, CO, United States;Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO, United States;Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States;Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO, United States;

关键词: islet;    T cell;    regulatory B cell;    resident lymphocyte;    type 2 diabetes;    type 1 diabetes;    tissue homeostasis;   

DOI  :  10.3389/fimmu.2022.814203

 received in 2021-11-12, accepted in 2022-01-04,  发布年份 2022

来源: Frontiers

【 摘 要 】

T cells and B cells have been identified in human and murine islets, but the phenotype and role of islet lymphocytes is unknown. Resident immune populations set the stage for responses to inflammation in the islets during homeostasis and diabetes. Thus, we sought to identify the phenotype and effector function of islet lymphocytes to better understand their role in normal islets and in islets under metabolic stress. Lymphocytes were located in the islet parenchyma, and were comprised of a mix of naïve, activated, and memory T cell and B cell subsets, with an enrichment for regulatory B cell subsets. Use of a Nur77 reporter indicated that CD8 T cells and B cells both received local antigen stimulus, indicating that they responded to antigens present in the islets. Analysis of effector function showed that islet T cells and B cells produced the regulatory cytokine IL-10. The regulatory phenotype of islet T cells and B cells and their response to local antigenic stimuli remained stable under conditions of metabolic stress in the diet induced obesity (DIO) model. T cells present in human islets retained a similar activated and memory phenotype in non-diabetic and T2D donors. Under steady-state conditions, islet T cells and B cells have a regulatory phenotype, and thus may play a protective role in maintaining tissue homeostasis.

【 授权许可】

Unknown   
Copyright © 2022 Whitesell, Lindsay, Olivas-Corral, Yannacone, Schoenbach, Lucas and Friedman