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


CONCLUSIONS
Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.
Son
Young Min
YM
Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Gwanak-gu, Seoul 151-921, Republic of Korea.
Ahn
Sung Min
SM
Kim
Gi Rak
GR
Moon
Yang Soo
YS
Kim
Sang Hoon
SH
Park
Yeong-Min
YM
Lee
Woon Kyu
WK
Min
Tae Sun
TS
Han
Seung Hyun
SH
Yun
Cheol-Heui
CH
D015704:CD4 Antigens / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D052243:Resistin / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D053645:Interleukin-2 Receptor alpha Subunit; D052243:Resistin; D016212:Transforming Growth Factor beta