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* Laboratory of Immunology and
Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; and
Singapore National Eye Center, Singapore
Noninfectious uveitis is a predominantly T cell-mediated autoimmune, intraocular inflammatory disease. To characterize the gene expression profile from patients with noninfectious uveitis, PBMCs were isolated from 50 patients with clinically characterized noninfectious uveitis syndrome. A pathway-specific cDNA microarray was used for gene expression profiling and real-time PCR array for further confirmation. Sixty-seven inflammation- and autoimmune-associated genes were found differentially expressed in uveitis patients, with 28 of those genes being validated by real-time PCR. Several genes previously unknown for autoimmune uveitis, including IL-22, IL-19, IL-20, and IL-25/IL-17E, were found to be highly expressed among uveitis patients compared with the normal subjects with IL-22 expression highly variable among the patients. Furthermore, we show that IL-22 can affect primary human retinal pigment epithelial cells by decreasing total tissue resistance and inducing apoptosis possibly by decreasing phospho-Bad level. In addition, the microarray data identified a possible uveitis-associated gene expression pattern, showed distinct gene expression profiles in patients during periods of clinical activity and quiescence, and demonstrated similar expression patterns in related patients with similar clinical phenotypes. Our data provide the first evidence that a subset of IL-10 family genes are implicated in noninfectious uveitis and that IL-22 can affect human retinal pigment epithelial cells. The results may facilitate further understanding of the molecular mechanisms of autoimmune uveitis and other autoimmune originated inflammatory diseases.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work is supported by the Intramural Research Program of the National Eye Institute.
2 Address correspondence and reprint requests to Dr. Robert B. Nussenblatt, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Building 10, Room 10N112, 9000 Rockville Pike, Bethesda, MD 20892. E-mail address: DrBob{at}nei.nih.gov
3 Abbreviations used in this paper: RPE, retinal pigment epithelial; qRT-PCR, quantitative RT-PCR; TER, total epithelial resistance; NL, normal.
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