Mast cells control lung type 2 inflammation via prostaglandin E2-driven soluble ST2

被引：11

作者：

Alhallak, Kinan ^{[1
,2
,3
]}

Nagai, Jun ^{[1
,2
,3
]}

Zaleski, Kendall ^{[3
]}

Marshall, Sofia ^{[3
]}

Salloum, Tamara ^{[1
,2
,3
]}

Derakhshan, Tahereh ^{[1
,2
,3
]}

Hayashi, Hiroaki ^{[1
,2
,3
]}

Feng, Chunli ^{[3
]}

Kratchmarov, Radomir ^{[1
,2
,3
]}

Lai, Juying ^{[3
]}

Kuchibhotla, Virinchi ^{[1
,2
,3
]}

Nishida, Airi ^{[3
]}

Balestrieri, Barbara ^{[1
,2
,3
]}

Laidlaw, Tanya ^{[1
,2
,3
]}

Dwyer, Daniel F. ^{[1
,2
,3
]}

Boyce, Joshua A. ^{[1
,2
,3
]}

机构：

[1] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[2] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Div Allergy & Clin Immunol, Jeff & Penny Vinik Ctr Allerg Dis Res, Boston, MA USA

来源：

IMMUNITY | 2024年 / 57卷 / 06期

关键词：

EXACERBATED RESPIRATORY-DISEASE; AIRWAY SMOOTH-MUSCLE; SEVERE ASTHMA; CHRONIC RHINOSINUSITIS; REDUCED EXPRESSION; NASAL POLYPS; PHASE; 2A; E-2; IL-33; RECEPTOR;

D O I：

10.1016/j.immuni.2024.05.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)33 signaling through its membrane -bound receptor, ST2. Soluble (s)ST2 reduces available IL -33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E-2 (PGE(2)) drives production of sST2 to limit features of lung T2I. PGE 2 -deficient mice display diminished sST2. In humans with severe respiratory T2I, urinary PGE(2) metabolites correlate with serum sST2. In mice, PGE(2) enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression by MCs, or E prostanoid (EP)(2) receptors by MCs showed reduced sST2 lung concentrations and strong T2I. Recombinant sST2 reduced T2I in mice lacking PGE 2 or ST2 expression by MCs back to control levels. PGE(2) deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expression by MCs. PGE(2) thus suppresses T2I through MC -derived sST2, explaining the severe T2I observed in low PGE(2) states.

引用

页码：1274 / 1288.e6

页数：22

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