Das Prodekanat für Forschung würdigt jeden Monat UKE Autorinnen und Autoren einer herausragenden Publikation, die in den vorangegangenen 2 Monaten hochrangig publiziert wurde. Ziel ist es, die am UKE enstandenen Forschungsergebnisse mit ihrer Bedeutung in der Wissenschaft einer größeren Öffentlichkeit am UKE vorzustellen. Der Aufruf zur Teilnahme richtet sich an Wissenschaftlerinnen und Wissenschaftler aller Fachgebiete. Einreichungsfrist für eine Bewerbung um die Auszeichnung des "Paper of the Month" ist jeweils Ende eines Monats (siehe Bewerbungsformular).
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UKE Paper of the Month March 2025
The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells
Nariaki Asada, Pauline Ginsberg, Hans-Joachim Paust, Ning Song, Jan-Hendrik Riedel, Jan-Eric Turner, Anett Peters, Anna Kaffke, Jonas Engeßer, Huiying Wang, Yu Zhao, Robin Khatri, Philipp Gild, Roland Dahlem, Björn-Philipp Diercks, Sarada Das, Zoya Ignatova, Tobias B. Huber, Immo Prinz, Nicola Gagliani, Hans-Willi Mittrücker, Christian F. Krebs, Ulf Panzer
ABSTRACT:
Tissue-resident memory T (Trm) cells are a specialized T cell population that resides in tissues and provides a rapid protective response upon activation. Here, we showed that human and mouse CD4+ Trm cells existed in a poised state and stored mRNAs encoding proinflammatory cytokines without protein production. At steady-state, cytokine mRNA translation in Trm cells was suppressed by the integrated stress response (ISR) pathway. Upon activation, the central ISR regulator, eIF2α, was dephosphorylated and stored cytokine mRNA was translated for immediate cytokine production. Genetic or pharmacological activation of the ISR-eIF2α pathway reduced cytokine production and ameliorated autoimmune kidney disease in mice. Consistent with these results, the ISR pathway in CD4+ Trm cells was downregulated in patients with immune-mediated diseases of the kidney and the intestine compared to healthy controls. Our results indicated that stored cytokine mRNA and translational regulation in CD4+ Trm cells facilitate rapid cytokine production during local immune response.
STATEMENT:
Our study demonstrates that CD4⁺ Trm cells store cytokine mRNA and, when activated, immediately produce cytokine protein.
BACKGROUND:
This work was led by Nariaki Asada, a Clinician Scientist at the UKE, and is the result of a long-standing collaboration between the groups of Ulf Panzer, Christian Krebs (both III. Department of Medicine), Hans-Willi Mittrücker (Institute of Immunology) and numerous other groups of the Hamburg Center of Translational Immunology. The project was funded by the DFG Collaborative Research Center 1192 “Immune-Mediated Glomerular Diseases”.
Nat Immunol. 2025 Apr;26 (4): 557-566
Congratulations to all authors!
Next PoM: To apply, the publication must have been published in April 2025. Applications will be considered in two rounds of the selection process, i.e. two months. Please send your completed PoM application to Dr. Anne Wulf by 30/04/2025.