期刊
CELLULAR IMMUNOLOGY
卷 285, 期 1-2, 页码 42-48出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2013.08.006
关键词
cAMP; TGF-beta; Adaptive Treg; MAPKs
资金
- National Natural Science Foundation of China [31270960, 31100544]
- National Key Technologies R & D Program for New Drugs [2013ZX09103003-010]
- National Key Basic Research Program of China [2010CB911904]
The second messenger cAMP is involved in the regulation of many cellular activities partially through modulating the MAPK pathways. The role of cAMP in TGF-beta-mediated adaptive Tregs differentiation remains elusive. In this work, we show that cAMP inhibits antigen-nonspecific proliferation of murine CD4+ T cells without significant promotion of apoptosis. Moreover, cAMP suppresses TGF-beta-induced expression of forkhead transcription factor Foxp3. 6-MB-cAMP, a site-selective activator of PKA, mimics the role of cAMP in TGF-beta-induced Foxp3 expression. Further exploration reveals that TGF-beta activates ERK and JNK, but not p38. cAMP and 6-MB-cAMP block TGF-beta-induced activation of ERK and JNK through transcription-independent manner and transcription-dependent manner, respectively. Since direct inhibition of ERK or JNK activity mimics the effects of cAMP during this process, our work suggests that cAMP suppresses TGF-beta-mediated adaptive Tregs differentiation through, at least partially, inhibiting the activation of ERK and JNK. (C) 2013 Elsevier Ltd. All rights reserved.
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