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Inflammasomes

IL-1α-releasing TH17 cells live long and prosper

Nature Immunology volume 24, pages 205–206 (2023)Cite this article

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TH17 cells combat infection but can also drive pathological inflammation. A TH17 cell NLRP3–caspase-8–caspase-3–GSDME axis is now shown to release the alarmin IL-1α without triggering cell death.

Deficiencies in inflammasome signaling can increase susceptibility to a wide range of pathogen infections, whereas excessive inflammasome activation can cause autoinflammatory diseases. Cytosolic inflammasome sensors, including several members of the NLR family (such as NLRP1, NLRC4 and NLRP3), detect and respond to specific pathogen-derived and host-derived danger molecules and initiate caspase-1-mediated activation of IL-1β and IL-18, as well as the pyroptotic effector GSDMD2. The plasma membrane GSDMD pore is a conduit for cytosolic molecules to escape from the cell3. These pores enable non-selective ionic flux and the release of appropriately sized cellular proteins, including mature IL-1β, IL-18 and damage-associated molecular patterns (DAMPs). One such DAMP is the IL-1 family member IL-1α, which does not require processing by caspase-1 for activation, but can be released from dying cells in a GSDMD-dependent manner to bind and activate the same IL-1 receptor (IL-1R) as IL-1β4.

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Fig. 1: TH17 TCR signaling induces and releases IL-1α via NLRP3 and GSDME in the absence of cell death.

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    Joanna R. Groom & James E. Vince

  2. The Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia

    Joanna R. Groom & James E. Vince

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  1. Joanna R. Groom
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  2. James E. Vince
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Correspondence to Joanna R. Groom or James E. Vince.

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Groom, J.R., Vince, J.E. IL-1α-releasing TH17 cells live long and prosper. Nat Immunol 24, 205–206 (2023). https://doi.org/10.1038/s41590-022-01412-x

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  • DOI: https://doi.org/10.1038/s41590-022-01412-x

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