Work

Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling Platforms in APCs

Year: 2018

Type: article

Abstract: 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-1β. 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-1β 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.

Source: The Journal of Immunology

DOI: 10.4049/jimmunol.1800505

Authors: Yifei Wang, Abigail L Sedlacek, Sudesh Pawaria, Haiyan Xu, Melanie J Scott, Robert J Binder

Institutions: University of Pittsburgh, Tsinghua University, University of Massachusetts Chan Medical School, Soochow University

Language: English

Topic: Inflammasome and immune disorders

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze