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Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice. Int J Mol Sci 2020 Dec 13;21(24)

Date

12/17/2020

Pubmed ID

33322152

Pubmed Central ID

PMC7764018

DOI

10.3390/ijms21249478

Scopus ID

2-s2.0-85097667415   3 Citations

Abstract

Sj??gren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.

Author List

Debreceni IL, Chimenti MS, Serreze DV, Geurts AM, Chen YG, Lieberman SM

Authors

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Autoimmunity
B-Lymphocytes
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 1
Disease Models, Animal
Female
Gene Expression Regulation
Inflammation
Interferon Type I
Lacrimal Apparatus
Male
Membrane Glycoproteins
Mice
Mice, Inbred NOD
Mice, Knockout
Salivary Glands
Sex
Sjogren's Syndrome
Toll-Like Receptor 7