Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling

被引：186

作者：

Bourdonnay, Emilie ^{[1
]}

Zaslona, Zbigniew ^{[1
]}

Penke, Loka Raghu Kumar ^{[1
]}

Speth, Jennifer M. ^{[1
]}

Schneider, Daniel J. ^{[1
]}

Przybranowski, Sally ^{[1
]}

Swanson, Joel A. ^{[2
]}

Mancuso, Peter ^{[3
]}

Freeman, Christine M. ^{[1
,4
]}

Curtis, Jeffrey L. ^{[1
,5
]}

Peters-Golden, Marc ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA

[4] Dept Vet Affairs Hlth Care Syst, Res Serv, Ann Arbor, MI 48105 USA

[5] Dept Vet Affairs Hlth Care Syst, Med Serv, Ann Arbor, MI 48105 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2015年 / 212卷 / 05期

基金：

美国国家卫生研究院;

关键词：

ALVEOLAR MACROPHAGES; MEMBRANE MICROPARTICLES; DENDRITIC CELLS; LUNG; SUPPRESSORS; PHAGOCYTOSIS; ACTIVATION; MECHANISMS; INHIBITION; INTERLEUKIN-1-BETA;

D O I：

10.1084/jem.20141675

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

JAK-STAT signaling mediates the actions of numerous cytokines and growth factors, and its endogenous brake is the family of SOCS proteins. Consistent with their intracellular roles, SOCS proteins have never been identified in the extracellular space. Here we report that alveolar macrophages can secrete SOCS1 and -3 in exosomes and microparticles, respectively, for uptake by alveolar epithelial cells and subsequent inhibition of STAT activation. Secretion is tunable and occurs both in vitro and in vivo. SOCS secretion into lung lining fluid was diminished by cigarette smoking in humans and mice. Secretion and transcellular delivery of vesicular SOCS proteins thus represent a new model for the control of inflammatory signaling, which is subject to dysregulation during states of inflammation.

引用

页码：729 / 742

页数：14

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