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. 2012 Nov;64(11):3564-73.
doi: 10.1002/art.34637.

Leptin Exacerbates Collagen-Induced Arthritis via Enhancement of Th17 Cell Response

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Leptin Exacerbates Collagen-Induced Arthritis via Enhancement of Th17 Cell Response

Jun Deng et al. Arthritis Rheum. .
Free article

Abstract

Objective: To determine the role of leptin in modulating Th17 cell response and joint inflammation in mice with collagen-induced arthritis (CIA).

Methods: Leptin receptor expression on T cells was examined by polymerase chain reaction (PCR) analysis, immunofluorescence microscopy, and flow cytometry. Effects of leptin on Th17 cell differentiation and proliferation were evaluated by quantitative PCR, carboxyfluorescein diacetate succinimidyl ester proliferation assay, and flow cytometry. Dynamic changes in leptin concentrations in the joint tissue and synovial fluid of mice with CIA were determined by immunohistochemistry analysis and enzyme-linked immunosorbent assay (ELISA). Arthritis symptoms and joint pathology in mice with CIA were assessed after injection of leptin into the knee joint. Th1 and Th17 cell populations in the spleen, draining lymph nodes, and joint tissue were analyzed by flow cytometry and enzyme-linked immunospot assay. Interleukin-17 messenger RNA and protein levels in the joint tissue were measured by PCR analysis and ELISA.

Results: In culture, leptin treatment significantly increased Th17 cell generation from naive CD4+ T cells. During CIA development, markedly elevated levels of leptin were detected in the joint tissue and synovial fluid. Moreover, injection of leptin into the knee joint of collagen-immunized mice resulted in an early onset of arthritis and substantially increased the severity of clinical symptoms, accompanied by more pronounced synovial hyperplasia and joint damage. Further examination by immunofluorescence microscopy confirmed the presence of significantly increased numbers of Th17 cells in the joint tissue and draining lymph nodes of leptin-treated mice with CIA.

Conclusion: The results of this study identify a previously undescribed function of leptin in enhancing Th17 cell response and exacerbating joint inflammation in mice with CIA.

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