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Open Access Highly Accessed Research article

Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

Young Min Son1, Sung Min Ahn1, Gi Rak Kim1, Yang Soo Moon2, Sang Hoon Kim3, Yeong-Min Park4, Woon Kyu Lee5, Tae Sun Min6, Seung Hyun Han7 and Cheol-Heui Yun1*

Author Affiliations

1 Protein Engineering and Comparative Immunology, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea

2 Molecular Biology, Department of Animal Science and Biotechnology, Jinju National University, Jinju 660-758, Republic of Korea

3 Animal Cell Physiology, Department of Biology, Kyung Hee University, Seoul 130-701, Republic of Korea

4 Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation and Regulation, Medical Research Institute, Pusan National University, College of Medicine, Busan, Republic of Korea

5 Center for Advanced Medical Education by BK21 project, College of Medicine, Inha University, Incheon 402-751, Republic of Korea

6 National Research Foundation of Korea, Daejeon 305-350, Republic of Korea

7 Department of Oral Microbiology & Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea

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BMC Immunology 2010, 11:33  doi:10.1186/1471-2172-11-33

Published: 30 June 2010

Abstract

Background

Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.

Results

Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin.

Conclusion

Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.