Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjögren syndrome

Scott M Lieberman; Portia A Kreiger; Gary A Koretzky

doi:10.1111/imm.12439

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Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjögren syndrome

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Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjögren syndrome

Scott M Lieberman, Portia A Kreiger and Gary A Koretzky

Immunology, Vol.145(2), pp.232-241

06/2015

DOI: 10.1111/imm.12439

PMCID: PMC4427388

PMID: 25581706

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Abstract

CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ-protective Treg cell functions have not been demonstrated in organ-specific autoimmunity. Non-obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well-characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male-specific, but the role of Treg cells in this sex-specificity is not known. This study aimed to determine if male-specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland-protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland-draining cervical lymph nodes of NOD mice to lymphocyte-deficient NOD-SCID mice. Transfer of bulk cervical lymph node cells modelled the male-specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4(+) CD25(+) Treg-enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male-specific factors promote reversible dysfunction of lacrimal gland-protective Treg cells and, to our knowledge, form the first evidence for reversible organ-protective Treg cell dysfunction in organ-specific autoimmunity.

Sjogren's Syndrome - pathology

Lacrimal Apparatus - immunology

Sjogren's Syndrome - immunology

Male

Dacryocystitis - immunology

Adoptive Transfer

Mice, SCID

T-Lymphocytes, Regulatory - pathology

T-Lymphocytes, Regulatory - immunology

Animals

Female

Mice, Inbred NOD

Mice

T-Lymphocytes, Regulatory - transplantation

Lacrimal Apparatus - pathology

Dacryocystitis - pathology

Disease Models, Animal

Details

Title: Subtitle: Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjögren syndrome
Creators: Scott M Lieberman - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Portia A Kreiger
Gary A Koretzky
Resource Type: Journal article
Publication Details: Immunology, Vol.145(2), pp.232-241
DOI: 10.1111/imm.12439
PMID: 25581706
PMCID: PMC4427388
ISSN: 0019-2805
eISSN: 1365-2567
Grant note: K12 HD043245 / NICHD NIH HHS K08 EY022344 / NEI NIH HHS 1S10 RR027219 / NCRR NIH HHS
Language: English
Date published: 06/2015
Academic Unit: Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
Record Identifier: 9984093229702771

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