胆酸
Jurkat细胞
骨化三醇受体
生物
免疫系统
MAPK/ERK通路
T细胞
信号转导
细胞生物学
获得性免疫系统
胆汁酸
FOXP3型
T细胞受体
受体
生物化学
免疫学
作者
Thijs W.H. Pols,Teresa Puchner,H. Inci Korkmaz,Mariska Vos,Maarten R. Soeters,Carlie J.M. de Vries
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2017-05-11
卷期号:12 (5): e0176715-e0176715
被引量:91
标识
DOI:10.1371/journal.pone.0176715
摘要
Bile acids are established signaling molecules next to their role in the intestinal emulsification and uptake of lipids. We here aimed to identify a potential interaction between bile acids and CD4+ Th cells, which are central in adaptive immune responses. We screened distinct bile acid species for their potency to affect T cell function. Primary human and mouse CD4+ Th cells as well as Jurkat T cells were used to gain insight into the mechanism underlying these effects. We found that unconjugated lithocholic acid (LCA) impedes Th1 activation as measured by i) decreased production of the Th1 cytokines IFNγ and TNFαα, ii) decreased expression of the Th1 genes T-box protein expressed in T cells (T-bet), Stat-1 and Stat4, and iii) decreased STAT1α/β phosphorylation. Importantly, we observed that LCA impairs Th1 activation at physiological relevant concentrations. Profiling of MAPK signaling pathways in Jurkat T cells uncovered an inhibition of ERK-1/2 phosphorylation upon LCA exposure, which could provide an explanation for the impaired Th1 activation. LCA induces these effects via Vitamin D receptor (VDR) signaling since VDR RNA silencing abrogated these effects. These data reveal for the first time that LCA controls adaptive immunity via inhibition of Th1 activation. Many factors influence LCA levels, including bile acid-based drugs and gut microbiota. Our data may suggest that these factors also impact on adaptive immunity via a yet unrecognized LCA-Th cell axis.
科研通智能强力驱动
Strongly Powered by AbleSci AI