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

• Published in: The Journal of experimental medicine Vol. 212; no. 5; pp. 729 - 742
• Main Authors: Bourdonnay, Emilie, Zasłona, Zbigniew, Penke, Loka Raghu Kumar, Speth, Jennifer M., Schneider, Daniel J., Przybranowski, Sally, Swanson, Joel A., Mancuso, Peter, Freeman, Christine M., Curtis, Jeffrey L., Peters-Golden, Marc
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 04.05.2015
• Subjects: Animals; Cell Line, Transformed; Cell-Derived Microparticles - immunology; Cell-Derived Microparticles - pathology; Epithelial Cells - immunology; Epithelial Cells - pathology; Female; Humans; Inflammation - immunology; Inflammation - pathology; Janus Kinases - immunology; Macrophages - immunology; Male; Mice; Pulmonary Alveoli - immunology; Pulmonary Alveoli - pathology; Rats; Rats, Wistar; Signal Transduction - immunology; STAT Transcription Factors - immunology; Suppressor of Cytokine Signaling Proteins - immunology
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20141675

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.