%0 Figure %A Zhou, Yu %A Wang, Wei %A Zhao, Conghui %A Wang, Yan %A Wu, Haoming %A Sun, Xiuyuan %A Guan, Youfei %A Zhang, Yu %D 2018 %T image_1.jpg %U https://frontiersin.figshare.com/articles/figure/image_1_jpg/5972128 %R 10.3389/fimmu.2018.00501.s001 %2 https://frontiersin.figshare.com/ndownloader/files/10710475 %K group 2 innate lymphoid cell %K prostaglandin E2 %K E-prostanoid 4 %K asthma %K IL-33 %K cyclic adenosine monophosphate %X

Evidence is accumulating that group 2 innate lymphoid cells (ILC2) play an important role in allergic airway inflammation by producing a large amount of type 2 cytokines. But it remains poorly understood how its activities are properly controlled in vivo. Here, we demonstrated that prostaglandin E2 (PGE2) had a profound inhibitory effect on IL-33-induced ILC2 expansion and IL-5 and IL-13 production in vitro. This effect was mimicked by PGE1-alcohol but attenuated by ONO-AE3-208, indicating a selective action through the E-prostanoid 4 (EP4) receptor. In the IL-33-induced asthma model, coadministration of PGE2 or PGE1-alcohol resulted in diminished IL-5 and IL-13 production, reduced eosinophilia and alleviated lung pathology. In contrast, EP4-deficient mice displayed an exacerbated inflammatory response in another ILC2-mediated asthma model induced by Alternaria extract. Mechanistic studies demonstrated that the PGE2-mediated inhibition of ILC2 was dependent on cyclic adenosine monophosphate (cAMP) production. Further downstream, PGE2-EP4-cAMP signaling led to suppression of GATA3 and ST2 expression, which is known to be critical for ILC2 activation. These findings reveal a novel function of PGE2 as a negative regulator of ILC2 activation and highlight an endogenous counter-regulatory mechanism for the control of innate allergic inflammatory responses.

%I Frontiers