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J Exp Med. 2015 May 4;212(5):729-42. doi: 10.1084/jem.20141675. Epub 2015 Apr 6.

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

Author information

1
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School; and Department of Environmental Health Sciences, School of Public Health; University of Michigan, Ann Arbor, MI 48109.
2
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School; and Department of Environmental Health Sciences, School of Public Health; University of Michigan, Ann Arbor, MI 48109 Research Services and Medical Services, Department of Veterans Affairs Health Care System, Ann Arbor, MI 48105.
3
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School; and Department of Environmental Health Sciences, School of Public Health; University of Michigan, Ann Arbor, MI 48109 petersm@umich.edu.

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.

PMID:
25847945
PMCID:
PMC4419346
DOI:
10.1084/jem.20141675
[Indexed for MEDLINE]
Free PMC Article

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