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Inflammasomes and adaptive immune responses

Abstract

A fundamental concept in immunology is that the innate immune system initiates or instructs downstream adaptive immune responses. Inflammasomes are central players in innate immunity to pathogens, but how inflammasomes shape adaptive immunity is complex and relatively poorly understood. Here we highlight recent work on the interplay between inflammasomes and adaptive immunity. We address how inflammasome-dependent release of cytokines and antigen activates, shapes or even inhibits adaptive immune responses. We consider how distinct tissue or cellular contexts may alter the effects of inflammasome activation on adaptive immunity and how this contributes to beneficial or detrimental outcomes in infectious diseases, cancer and autoimmunity. We aspire to provide a framework for thinking about inflammasomes and their connection to the adaptive immune response.

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Fig. 1: Schematic of events following canonical and noncanonical inflammasome activation.
Fig. 2: Proposed models of how pyroptotic cells in tissues or in the intestinal epithelium may provide the three signals required for activation of naive T cells.

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Acknowledgements

Research in R.E.V.’s lab is supported by an Investigator Award from the Howard Hughes Medical Institute and by National Institutes of Health grant nos. AI063302, AI075039 and AI155634. Additionally, the authors thank M. Gaidt, I. Rauch and D. Kotov for providing invaluable scientific insights and editorial feedback.

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R.E.V. is a consultant for Ventus Therapeutics.

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Deets, K.A., Vance, R.E. Inflammasomes and adaptive immune responses. Nat Immunol 22, 412–422 (2021). https://doi.org/10.1038/s41590-021-00869-6

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