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Prostaglandin E(2) Inhibits Group 2 Innate Lymphoid Cell Activation and Allergic
Airway Inflammation Through E-Prostanoid 4-Cyclic Adenosine Monophosphate
Signaling
#MMPMID29593738
Zhou Y
; Wang W
; Zhao C
; Wang Y
; Wu H
; Sun X
; Guan Y
; Zhang Y
Front Immunol
2018[]; 9
(?): 501
PMID29593738
show ga
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 E(2)
(PGE(2)) 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 PGE(1)-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 PGE(2) or PGE(1)-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 PGE(2)-mediated inhibition of ILC2 was dependent on
cyclic adenosine monophosphate (cAMP) production. Further downstream,
PGE(2)-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 PGE(2) as a negative regulator of ILC2 activation and highlight an
endogenous counter-regulatory mechanism for the control of innate allergic
inflammatory responses.
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