Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

Ivy L Debreceni; Michael S Chimenti; David V Serreze; Aron M Geurts; Yi-Guang Chen; Scott M Lieberman

doi:10.3390/ijms21249478

Back

Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

Journal article

Open access

Peer reviewed

Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

Ivy L Debreceni, Michael S Chimenti, David V Serreze, Aron M Geurts, Yi-Guang Chen and Scott M Lieberman

International journal of molecular sciences, Vol.21(24), pp.1-19

12/13/2020

DOI: 10.3390/ijms21249478

PMCID: PMC7764018

PMID: 33322152

Files and links (1)

url

https://doi.org/10.3390/ijms21249478View

Published (Version of record) Open Access

Abstract

Sjögren 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 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.

Animals

Autoimmunity - genetics

B-Lymphocytes - immunology

Diabetes Mellitus, Experimental - metabolism

Diabetes Mellitus, Type 1 - metabolism

Disease Models, Animal

Female

Gene Expression Regulation - immunology

Inflammation - genetics

Inflammation - immunology

Inflammation - pathology

Interferon Type I - metabolism

Lacrimal Apparatus - cytology

Lacrimal Apparatus - immunology

Lacrimal Apparatus - pathology

Male

Membrane Glycoproteins - genetics

Membrane Glycoproteins - immunology

Mice

Mice, Inbred NOD

Mice, Knockout

RNA-Seq

Salivary Glands - cytology

Salivary Glands - immunology

Salivary Glands - metabolism

Sex

Sjogren's Syndrome - immunology

Toll-Like Receptor 7 - genetics

Toll-Like Receptor 7 - immunology

Details

Title: Subtitle: Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice
Creators: Ivy L Debreceni - University of Iowa
Michael S Chimenti - University of Iowa
David V Serreze - Jackson Laboratory
Aron M Geurts - Medical College of Wisconsin
Yi-Guang Chen - Medical College of Wisconsin
Scott M Lieberman - Immunology Graduate Program, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.21(24), pp.1-19
DOI: 10.3390/ijms21249478
PMID: 33322152
PMCID: PMC7764018
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Grant note: R01 DK121747 / NIDDK NIH HHS Innovator Fund award 20-08 / Jackson Laboratory DK097605 / NIH HHS P30 CA034196 / NCI NIH HHS T32 AI07485 / NIH HHS R01 DK107541 / NIDDK NIH HHS EY027731 / NIH HHS R21 AI144360 / NIAID NIH HHS OD030187 / NIH HHS DP3 DK097605 / NIDDK NIH HHS R01 EY027731 / NEI NIH HHS DK095735 / NIH HHS
Language: English
Date published: 12/13/2020
Academic Unit: Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology; Iowa Institute of Human Genetics
Record Identifier: 9984354007802771

Metrics

17 Record Views

16 Times Cited - Web of Science