Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response
Article first published online: 27 OCT 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 11, pages 3564–3573, November 2012
How to Cite
Deng, J., Liu, Y., Yang, M., Wang, S., Zhang, M., Wang, X., Ko, K.-H., Hua, Z., Sun, L., Cao, X. and Lu, L. (2012), Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response. Arthritis & Rheumatism, 64: 3564–3573. doi: 10.1002/art.34637
- Issue published online: 27 OCT 2012
- Article first published online: 27 OCT 2012
- Accepted manuscript online: 25 JUL 2012 09:54AM EST
- Manuscript Accepted: 12 JUL 2012
- Manuscript Received: 24 MAR 2012
- National Basic Research Program of China. Grant Number: 2010 CB 529100
- Nanjing University State Key Laboratory of Pharmaceutical Biotechnology. Grant Number: KF-GN-201102
- Hong Kong Research Grants Council
- National Natural Science Foundation of China. Grant Numbers: 30871193, 81072453, 31100648, 30910103087
- Senior Research Fellowship from the Croucher Foundation, Hong Kong
To determine the role of leptin in modulating Th17 cell response and joint inflammation in mice with collagen-induced arthritis (CIA).
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.
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.
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.