Department of Medicine
Immunology and Infectious Disease
Several heat shock proteins (HSPs) prime immune responses, which are, in part, a result of activation of APCs. APCs respond to these immunogenic HSPs by upregulating costimulatory molecules and secreting cytokines, including IL-1beta. These HSP-mediated responses are central mediators in pathological conditions ranging from cancer, sterile inflammation associated with trauma, and rheumatoid arthritis. We tested in this study the requirement of inflammasomes in the release of IL-1beta by one immunogenic HSP, gp96. Our results show that murine APCs activate NLRP3 inflammasomes in response to gp96 by K(+) efflux. This is shown to initiate inflammatory conditions in vivo in the absence of additional known inflammasome activators or infection. These results document a novel mechanism by which proteins of endogenous origin, the HSPs, can modulate an inflammatory response following their release from aberrant cells.
heat shock proteins, immune responses, cytokines
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Copyright © 2018 by The American Association of Immunologists, Inc. Publisher's PDF posted as allowed by publisher's Author Choice policy at: http://www.jimmunol.org/info/authorchoice.
DOI of Published Version
J Immunol. 2018 Oct 15;201(8):2209-2214. doi: 10.4049/jimmunol.1800505. Epub 2018 Sep 12. Link to article on publisher's site
Journal of immunology (Baltimore, Md. : 1950)
Wang Y, Sedlacek AL, Pawaria S, Xu H, Scott MJ, Binder RJ. (2018). Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling Platforms in APCs. Open Access Articles. https://doi.org/10.4049/jimmunol.1800505. Retrieved from https://escholarship.umassmed.edu/oapubs/3603