Age-related T-cell cytokine profile parallels corneal disease severity in Sjogren's syndrome-like keratoconjunctivitis sicca in CD25KO mice.
OBJECTIVE
IL-2ralpha (CD25)(-/-) mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice.


METHODS
CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears.


RESULTS
Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4(+) and CD8(+) T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-beta1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-gamma mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-gamma spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4(+) T cell infiltrating the cornea.


CONCLUSIONS
Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression.
De Paiva
Cintia S
CS
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA. cintiadp@bcm.tmc.edu
Hwang
Cindy S
CS
Pitcher
John D
JD
Pangelinan
Solherny B
SB
Rahimy
Ehsan
E
Chen
Wei
W
Yoon
Kyung-Chul
KC
Farley
William J
WJ
Niederkorn
Jerry Y
JY
Stern
Michael E
ME
Li
De-Quan
DQ
Pflugfelder
Stephen C
SC
D000375:Aging / Q000276:immunology; D000818:Animals; D017209:Apoptosis; D003228:Conjunctiva / Q000276:immunology; D003315:Cornea / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency / Q000276:immunology; D007638:Keratoconjunctivitis Sicca / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013666:Tears / Q000276:immunology
D016207:Cytokines; C508018:Il2ra protein, mouse; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit