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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)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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)