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E. Furusato, D. Shen, X. Cao, J. D. Cameron, C.-C. Chan, E. J. Rushing; T Cells Express IFN- and IL-17, Macrophages Express CXCL11 and IL-23 in Orbital and Neuro- Sarcoidosis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3766.
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© ARVO (1962-2015); The Authors (2016-present)
Sarcoidosis is a multisystem disease of unknown etiology characterized histologically by the presence of noncaseating granulomas in affected organs. Recently, T helper (Th) lymphocytes have been subdivided into Th1 (IL-2 and IFN-γ), Th2 (IL-4, IL-5, and IL-10), and Th17 (IL-17 and IL-22) subsets, while macrophages polarize to M1 (CCL19, CXCL11, and IL-23) and M2 (CCL17 and CCL22) subtypes. This study aims to identify the chemokine and cytokine expression profile in orbital- and neuro-sarcoidosis.
Inflammatory foci composed of noncaseating granulomas and lymphocytic collections outside granulomas were separately microdissected from archived, paraffin-embedded slides of 9 cases, including 4 cases of neuro- sarcoidosis and 5 of orbital sarcoidosis. RNA was extracted and QT-PCR was performed for IFN-γ, IL-17, IL-18, IL-23, CXCL11, and CCL17 transcripts.
All cases demonstrated classical noncaseating granulomatous inflammation and collections of nongranulomatous lymphocytes within brain or orbital tissue. Compared to the human universal mRNA value as 1, IFN-γ expressionwithin lymphocytes and granulomas was 1.7 and 0.04, IL-17 was 754 and absent, respectively. This result indicates that IFN-γ andIL-17 were mainly lymphocyte- derived (Th1 and Th17) cytokines. Alternatively, cells within granulomas expressed mainly IL-23 (2.6) and CXCL11 (9) compared to IL-23 (0.004) and CXCL11 (0.84) within lymphocytes outside granulomas, consistent with mainly M1 macrophage-derived chemokines and cytokines. However, IL-18 expression was not significantly different within the two populations. CCL17 expression (142) was mainly restricted to nongranulomatous lymphocytes.
Our data suggest that the induction and evolution of granuloma formation in orbital- and neuro-sarcoidosis may result from the complex interplay of diverse cell types (Th1, Th17, and M1 cells), and their accompanying cytokines and chemokines. Thus, activated Th1 and Th17 lymphocytes outside noncaseating granulomas and activated M1 macrophages within granulomas release cytokines and chemokines that contribute to the pathogenesis of sarcoidosis. Therefore, effective therapy for orbital- and neuro-sarcoidosis may benefit from specific targeting of Th1, Th17, and M1 cells, and their respective cytokines and chemokines.
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