Desiccating stress induces T cell-mediated Sjögren's Syndrome-like lacrimal keratoconjunctivitis.
Chronic dry eye syndrome affects over 10 million people in the United States; it is associated with inflammation of the lacrimal gland (LG) and in some cases involves T cell infiltration of the conjunctiva. We demonstrate that environmental desiccating stress (DS) elicits T cell-mediated inflammation of the cornea, conjunctiva, and LG, but not other organs in mice. The lacrimal keratoconjunctivitis (LKC) was mediated by CD4(+) T cells, which, when adoptively transferred to T cell-deficient nude mice, produced inflammation in the LG, cornea, and conjunctiva, but not in any other organ. Adoptively transferred CD4(+) T cells produced LKC even though recipients were not exposed to DS. LKC was exacerbated in euthymic mice depleted of CD4(+)CD25(+)forkhead/winged helix transcription factor(+) regulatory T cells. The results suggest that DS exposes shared epitopes in the cornea, conjunctiva, and LG that induce pathogenic CD4(+) T cells that produce LKC, which under normal circumstances is restrained by CD4(+)CD25(+)forkhead/winged helix transcription factor(+) regulatory T cells.
Niederkorn
Jerry Y
JY
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, 75390, USA. jerry.niederkorn@utsouthwestern.edu
Stern
Michael E
ME
Pflugfelder
Stephen C
SC
De Paiva
Cintia S
CS
Corrales
Rosa M
RM
Gao
Jianping
J
Siemasko
Karyn
K
D000818:Animals; D002465:Cell Movement; D003681:Dehydration / Q000150:complications / Q000503:physiopathology*; D003890:Desiccation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007638:Keratoconjunctivitis Sicca / Q000276:immunology* / Q000473:pathology; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology*; D051379:Mice; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse