Age-related T-cell cytokine profile parallels corneal disease severity in Sjogren's syndrome-like keratoconjunctivitis sicca in CD25KO mice.

Abstract

OBJECTIVES:

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.

• Authors: Cintia S De Paiva, Cindy S Hwang, John D Pitcher 3rd, Solherny B Pangelinan, Ehsan Rahimy, Wei Chen, Kyung-Chul Yoon, William J Farley, Jerry Y Niederkorn, Michael E Stern, De-Quan Li, Stephen C Pflugfelder
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 49 Issue 2 Pg. 246-58 (Feb 2010) ISSN: 1462-0332 [Electronic] England
• PMID: 20007286 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Il2ra protein, mouse
• Inflammation Mediators
• Interleukin-2 Receptor alpha Subunit

Topics

• Aging (immunology)
• Animals
• Apoptosis
• Conjunctiva (immunology)
• Cornea (immunology)
• Cytokines (metabolism)
• Epithelium, Corneal (immunology, pathology, physiopathology)
• Inflammation Mediators (metabolism)
• Interleukin-2 Receptor alpha Subunit (deficiency, immunology)
• Keratoconjunctivitis Sicca (immunology, pathology, physiopathology)
• Lacrimal Apparatus (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Permeability
• Sjogren's Syndrome (immunology, pathology, physiopathology)
• T-Lymphocyte Subsets (immunology)
• Tears (immunology)