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Chao, Y.Y.* ; Puhach, A.* ; Frieser, D.* ; Arunkumar, M.* ; Lehner, L.* ; Seeholzer, T. ; Garcia-Lopez, A.* ; van der Wal, M.* ; Fibi-Smetana, S.* ; Dietschmann, A.* ; Sommermann, T.* ; Cikovic, T.* ; Taher, L.* ; Gresnigt, M.S.* ; Vastert, S.J.* ; van Wijk, F.* ; Panagiotou, G.* ; Krappmann, D. ; Groß, O.* ; Zielinski, C.E.*

Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation.

Nat. Immunol. 24:33 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
It has been shown that innate immune responses can adopt adaptive properties such as memory. Whether T cells utilize innate immune signaling pathways to diversify their repertoire of effector functions is unknown. Gasdermin E (GSDME) is a membrane pore-forming molecule that has been shown to execute pyroptotic cell death and thus to serve as a potential cancer checkpoint. In the present study, we show that human T cells express GSDME and, surprisingly, that this expression is associated with durable viability and repurposed for the release of the alarmin interleukin (IL)-1α. This property was restricted to a subset of human helper type 17 T cells with specificity for Candida albicans and regulated by a T cell-intrinsic NLRP3 inflammasome, and its engagement of a proteolytic cascade of successive caspase-8, caspase-3 and GSDME cleavage after T cell receptor stimulation and calcium-licensed calpain maturation of the pro-IL-1α form. Our results indicate that GSDME pore formation in T cells is a mechanism of unconventional cytokine release. This finding diversifies our understanding of the functional repertoire and mechanistic equipment of T cells and has implications for antifungal immunity.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Secretion; Effector; Protease; Interleukin-1-beta; Differentiation; Identification; Mechanisms; Il-1-alpha; Pyroptosis; Regulator
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Journal Nature Immunology
Quellenangaben Volume: 24, Issue: 2, Pages: , Article Number: 33 Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Grants European Research Council (ERC)
European Research Council
Carl-Zeiss Stiftung
German Center of Infection Research
Emmy Noether Program
Germany's Excellence Strategy (Balance of the Microverse)
Leibniz Center for Photonics in Infection Research
Deutsche Forschungsgemeinschaft (German Research Foundation)