Signed, Sealed, Delivered

Unconventional secretion and subsequent uptake of molecular cargo via extracellular vesicles (EVs) is an important mechanism by which cells can exert paracrine effects. While this phenomenon has been widely characterized in the context of their ability to promote inflammation, less is known about the ability of EVs to transfer immunosuppressive cargo. Maintenance of normal physiology in the lung requires suppression of potentially damaging inflammatory responses to the myriad of insults to which it is continually exposed.

Recently, researchers from the University of Michigan Medical School reported the ability of alveolar macrophages (AMs) to secrete suppressors of cytokine signaling (SOCS) proteins within microvesicles (MVs) and exosomes (Exos). Uptake of these EVs by alveolar epithelial cells (AECs) resulted in inhibition of pro-inflammatory STAT activation in response to cytokines. Moreover, AM packaging of SOCS within EVs could be rapidly tuned in response to exogenous or AEC-derived substances.  Advances in these areas are critical for improving understanding of intercellular communication in the immune system and for therapeutic application of artificial vesicles aimed at treatment of diseases characterized by dysregulated inflammation.

AM and AEC crosstalk in the lung

exosomes

AMs release Exos and MVs containing SOCS1 and SOCS3, respectively. Positive regulators of SOCS release include the bioactive lipid PGE2, the cytokine IL-10, and AEC-derived mediators in response to LPS and infection. Negative regulators include acute, direct AM exposure of LPS, and cigarette smoke. AEC uptake of SOCS-containing EVs might likewise be modulated by constituents of the normal alveolar milieu or by exogenous factors to which the lung is exposed. Additionally, EV uptake by AECs results in inhibition of cytokine-induced STAT activation.

Schneider DJ, Speth JM, Peters-Golden M. (2016) Signed, Sealed, Delivered: Microenvironmental Modulation of Extracellular Vesicle-Dependent Immunoregulation in the Lung. Front Cell Dev Biol [Epub ahead of print]. [article]

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