Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjögren Syndrome

Yury Chaly; Jennifer Y Barr; David A Sullivan; Helen E Thomas; Thomas C Brodnicki; Scott M Lieberman

doi:10.3390/ijms19103259

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Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjögren Syndrome

Journal article

Open access

Peer reviewed

Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjögren Syndrome

Yury Chaly, Jennifer Y Barr, David A Sullivan, Helen E Thomas, Thomas C Brodnicki and Scott M Lieberman

International journal of molecular sciences, Vol.19(10), p.3259

10/20/2018

DOI: 10.3390/ijms19103259

PMCID: PMC6214106

PMID: 30347820

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Abstract

Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sjögren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines ( , ) and other potentially disease-relevant genes ( , ) were upregulated in male lacrimal glands. Expression of and , in particular, remained significantly upregulated in the lacrimal glands of lymphocyte-deficient NOD-severe combined immunodeficiency (SCID) mice and their expression was modulated by type I interferon signaling. Notably, -deficient NOD mice did not develop dacryoadenitis. Together these data identify disease-relevant genes upregulated in the context of male-specific dacryoadenitis and demonstrate a requisite role for type I interferon signaling in lacrimal gland autoimmunity in NOD mice.

Animals

Cells, Cultured

Chemokine CCL19 - metabolism

Chemokine CXCL9 - metabolism

Dacryocystitis - metabolism

Female

Interferon Type I - metabolism

Lacrimal Apparatus - metabolism

Lacrimal Apparatus - pathology

Male

Mice

Mice, Inbred NOD

Mice, SCID

Signal Transduction

Sjogren's Syndrome - metabolism

T-Lymphocytes, Regulatory - metabolism

Details

Title: Subtitle: Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjögren Syndrome
Creators: Yury Chaly - Roy J. and Lucille A. Carver College of Medicine
Jennifer Y Barr - Roy J. and Lucille A. Carver College of Medicine
David A Sullivan - Massachusetts Eye and Ear Infirmary
Helen E Thomas - The University of Melbourne
Thomas C Brodnicki - The University of Melbourne
Scott M Lieberman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA. scott-lieberman@uiowa.edu
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.19(10), p.3259
DOI: 10.3390/ijms19103259
PMID: 30347820
PMCID: PMC6214106
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Grant note: 1042735 / National Health and Medical Research Council R01 EY027731 / NEI NIH HHS EY05612 / National Institutes of Health EY027731 / National Institutes of Health 1037321 / National Health and Medical Research Council
Language: English
Date published: 10/20/2018
Academic Unit: Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
Record Identifier: 9984354049802771

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