Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function

Huang, Juan, Peng, Jian, Pearson, James Alexander ORCID: https://orcid.org/0000-0002-2867-2269, Efthimiou, Georgios, Hu, Youjia, Tai, Ningwen, Xing, Yanpeng, Zhang, Luyao, Gu, Jianlei, Jiang, Jianping, Zhao, Hongyu, Zhou, Zhiguang, Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845 and Wen, Li 2021. Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function. Cellular and Molecular Immunology 18 , pp. 328-338. 10.1038/s41423-020-00590-8

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (3MB) | Preview

Abstract

Innate immunity mediated by Toll-like receptors (TLRs), which can recognize pathogen molecular patterns, plays a critical role in type 1 diabetes development. TLR7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells; however, its role in type 1 diabetes development remains unclear. In our study, we discovered that Tlr7-deficient (Tlr7−/−) nonobese diabetic (NOD) mice, a model of human type 1 diabetes, exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient (Tlr7+/+) NOD mice. Mechanistic investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin production. Moreover, Tlr7−/− NOD B cells were found to suppress diabetogenic CD4+ T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T cells. In addition, we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8+ T-cell activation by downregulating the expression of both nonclassical and classical MHC class I (MHC-I) molecules on B cells. Our data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T cells. Therefore, therapeutically targeting TLR7 may prove beneficial for disease protection.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Nature Publishing Group
ISSN:	1672-7681
Funders:	MRC, JDRF, NIH
Date of First Compliant Deposit:	15 January 2021
Date of Acceptance:	31 October 2020
Last Modified:	03 May 2023 18:41
URI:	https://orca.cardiff.ac.uk/id/eprint/137704

Citation Data

Cited 13 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item