BACKGROUND Sarcoidosis is a systemic granulomatous disease characterized by the combination of Th1 and Th17 responses. Recently, several arguments have suggested a potential involvement of B cells as well as… Click to show full abstract
BACKGROUND Sarcoidosis is a systemic granulomatous disease characterized by the combination of Th1 and Th17 responses. Recently, several arguments have suggested a potential involvement of B cells as well as T cells in the pathogenesis of sarcoidosis. Follicular helper CD4+ T (TFH) cells are specialized in interacting with and helping B cells, and play a crucial role in the formation of germinal centers. OBJECTIVE We sought to explore the status of TFH cells and investigate their possible pathogenic role in sarcoidosis. METHODS TFH cells and B cells in peripheral blood were examined by flow cytometry, and serum samples were studied by cytokine arrays. Immunohistochemistry was performed to check for the presence of TFH cells in sarcoidosis skin lesions. Gene expression in isolated TFH cells was analyzed by quantitative RT-PCR. RESULTS The proportion of circulating TFH cells was decreased. CD4+CXCR5+ TFH cells were observed in cutaneous lesions in sarcoidosis. Gene expression in circulating TFH cells and serum cytokine concentrations related to Th17 were increased in sarcoidosis patients. Gene expressions of B cell differentiation cytokines in TFH cells were not altered in sarcoidosis patients. CONCLUSION We herein describe a decrease of circulating TFH cells and their migration to affected tissues. Circulating TFH cells are one of the potential cell types capable of producing IL-17 and enhancing Th17 responses, and may promote the chronic inflammation. We could not demonstrate a direct linkage between the imbalance of TFH cells and abnormal B cell differentiation in sarcoidosis.
               
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