Transcellular Delivery of Vesicular SOCS Proteins from Macrophages to Epithelial Cells Blunts Inflammatory Signaling

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2015 Apr 8

PMID 25847945

Citations 122

Authors

Emilie Bourdonnay

Zbigniew Zaslona

Loka Raghu Kumar Penke

Jennifer M Speth

Daniel J Schneider

Sally Przybranowski

Joel A Swanson

Peter Mancuso

Christine M Freeman

Jeffrey L Curtis

Marc Peters-Golden

Affiliations

Soon will be listed here.

Abstract

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.

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