Title | Interleukin-1 as a phenotypic immunomodulator in keratinizing squamous metaplasia of the ocular surface in Sjögren's syndrome. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Chen Y-T, Nikulina K, Lazarev S, Bahrami AF, Noble LB, Gallup M, McNamara NA |
Journal | Am J Pathol |
Volume | 177 |
Issue | 3 |
Pagination | 1333-43 |
Date Published | 2010 Sep |
ISSN | 1525-2191 |
Keywords | Animals, Cell Count, Eye, Eye Diseases, Humans, Immunohistochemistry, Interleukin-1, Metaplasia, Mice, Mice, Transgenic, Reverse Transcriptase Polymerase Chain Reaction, Sjogren's Syndrome |
Abstract | Chronic inflammation of the ocular surface in Sjögren's syndrome (SS) is associated with a vision-threatening, phenotypic change of the ocular surface, which converts from a nonkeratinized, stratified squamous epithelium to a nonsecretory, keratinized epithelium. This pathological process is known as squamous metaplasia. Based on a significant correlation between ocular surface interleukin (IL)-1beta expression and squamous metaplasia in patients with SS, we investigated the role of IL-1 in the pathogenesis of squamous metaplasia in an animal model that mimics the clinical characteristics of SS. Using autoimmune-regulator (aire)-deficient mice, we assessed lacrimal gland and ocular surface immunopathology by quantifying the infiltration of major histocompatibility complex class II(+) (I-A(d+)) dendritic cells and CD4(+) T cells. We examined squamous metaplasia using a biomarker of keratinization, small proline-rich protein 1B. We used lissamine green staining as a readout for ocular surface epitheliopathy and Alcian blue/periodic acid-Schiff histochemical analysis to characterize goblet cell muco-glycoconjugates. Within 8 weeks, the eyes of aire-deficient mice were pathologically keratinized with significant epithelial damage and altered mucin glycosylation. Although knockdown of IL-1 receptor 1 did not attenuate lymphocytic infiltration of the lacrimal gland or eye, it significantly reduced ocular surface keratinization, epitheliopathy, and muco-glycoconjugate acidification. These data demonstrate a phenotypic modulation role for IL-1 in the pathogenesis of squamous metaplasia and suggest that IL-1 receptor 1-targeted therapies may be beneficial for treating ocular surface disease associated with SS. |
DOI | 10.2353/ajpath.2010.100227 |
Alternate Journal | Am. J. Pathol. |
PubMed ID | 20696775 |
PubMed Central ID | PMC2928966 |
Grant List | R01-EY016203 / EY / NEI NIH HHS / United States R01 CA094143 / CA / NCI NIH HHS / United States R01 EY016203 / EY / NEI NIH HHS / United States EY02162 / EY / NEI NIH HHS / United States 3R01-EY016203-04S1 / EY / NEI NIH HHS / United States P30 EY002162 / EY / NEI NIH HHS / United States |
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