Open AccessIL-37b suppresses T cell priming by modulating dendritic cell maturation and cytokine production via dampening ERK/NF-κB/S6K signalings
Author(s) -
Wantong Wu,
Weiqiang Wang,
Yun Wang,
Wenwen Li,
Gang Yu,
Zhonglong Li,
Chunmin Fang,
Yue Shen,
Zhina Sun,
Leng Han,
Juan Yu,
Lijun Fang,
Song Chen,
Kui Dong,
Han Han,
Hanzhi Liu,
Yuechen Luo,
Xiaoming Feng
Publication year - 2015
Publication title -
acta biochimica et biophysica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1093/abbs/gmv058
Subject(s) - cd80 , mapk/erk pathway , microbiology and biotechnology , cytokine , cd86 , t cell , dendritic cell , priming (agriculture) , nf κb , signal transduction , p70 s6 kinase 1 , pi3k/akt/mtor pathway , immune system , chemistry , biology , immunology , cd40 , in vitro , biochemistry , cytotoxic t cell , germination , botany
Interleukin 37b (IL-37b) plays a key role in suppressing immune responses, partially by modulating the function of dendritic cells (DCs). However, the precise mechanisms are still largely unknown. Here, we investigated the effects of IL-37b on DC maturation and T cell responses induced by DCs, and explored the involved signaling pathways. It was found that IL-37b down-regulated the expressions of co-stimulatory molecules CD80 and CD86 on DCs in vitro. At the same time, the expressions of pro-inflammatory cytokines, such as TNF-α and IL-6, were suppressed, while the expression of the T cell inhibitory cytokine TGF-β was increased in IL-37b-treated DCs. In addition, the activation effect of DCs on T cells was impaired by IL-37b. We further revealed that extracellular single-regulated kinase (ERK), nuclear factor-κB (NF-κB), and mTOR-S6K signaling pathways were involved in the inhibition of DCs induced by IL-37b. This was confirmed by the similarly suppressive effect of chemical inhibitors against NF-κB, ERK, and S6K on the expressions of IL-6 and TNF-α in DCs. In conclusion, these results demonstrated that IL-37b suppressed DC maturation and immunostimulatory capacity in T cell priming by involving in ERK, NF-κB, and S6K-based inhibitory signaling pathways.