Non-redundant functions of group 2 innate lymphoid cells

Katja J. Jarick, Patrycja M. Topczewska, Manuel O. Jakob, Hiroshi Yano, Mohammad Arifuzzaman, Xuemei Gao, Sotiria Boulekou, Vladislava Stokic-Trtica, Pierre S. Leclère, Alexandra Preußer, Zoe A. Rompe, Anton Stamm, Amy M. Tsou, Coco Chu, Frederik R. Heinrich, Gabriela M. Guerra, Pawel Durek, Andranik Ivanov, Dieter Beule, Sofia Helfrich, Claudia U. Duerr, Anja A. Kühl, Christina Stehle, Chiara Romagnani, Mir-Farzin Mashreghi, Andreas Diefenbach, David Artis and Christoph S. N. Klose ()
Additional contact information
Katja J. Jarick: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Patrycja M. Topczewska: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Manuel O. Jakob: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Hiroshi Yano: Weill Cornell Medicine
Mohammad Arifuzzaman: Weill Cornell Medicine
Xuemei Gao: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Sotiria Boulekou: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Vladislava Stokic-Trtica: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Pierre S. Leclère: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Alexandra Preußer: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Zoe A. Rompe: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Anton Stamm: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Amy M. Tsou: Weill Cornell Medicine
Coco Chu: Weill Cornell Medicine
Frederik R. Heinrich: an Institute of the Leibniz Association
Gabriela M. Guerra: an Institute of the Leibniz Association
Pawel Durek: an Institute of the Leibniz Association
Andranik Ivanov: Berlin Institute of Health at Charité–Universitätsmedizin Berlin
Dieter Beule: Berlin Institute of Health at Charité–Universitätsmedizin Berlin
Sofia Helfrich: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Claudia U. Duerr: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Anja A. Kühl: Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Christina Stehle: an Institute of the Leibniz Association
Chiara Romagnani: an Institute of the Leibniz Association
Mir-Farzin Mashreghi: an Institute of the Leibniz Association
Andreas Diefenbach: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
David Artis: Weill Cornell Medicine
Christoph S. N. Klose: Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin

Nature, 2022, vol. 611, issue 7937, 794-800

Abstract: Abstract Protective immunity relies on the interplay of innate and adaptive immune cells with complementary and redundant functions. Innate lymphoid cells (ILCs) have recently emerged as tissue-resident, innate mirror images of the T cell system, with which they share lineage-specifying transcription factors and effector machinery1. Located at barrier surfaces, ILCs are among the first responders against invading pathogens and thus could potentially determine the outcome of the immune response2. However, so far it has not been possible to dissect the unique contributions of ILCs to protective immunity owing to limitations in specific targeting of ILC subsets. Thus, all of the available data have been generated either in mice lacking the adaptive immune system or with tools that also affect other immune cell subsets. In addition, it has been proposed that ILCs might be dispensable for a proper immune response because other immune cells could compensate for their absence3–7. Here we report the generation of a mouse model based on the neuromedin U receptor 1 (Nmur1) promoter as a driver for simultaneous expression of Cre recombinase and green fluorescent protein, which enables gene targeting in group 2 ILCs (ILC2s) without affecting other innate and adaptive immune cells. Using Cre-mediated gene deletion of Id2 and Gata3 in Nmur1-expressing cells, we generated mice with a selective and specific deficiency in ILC2s. ILC2-deficient mice have decreased eosinophil counts at steady state and are unable to recruit eosinophils to the airways in models of allergic asthma. Further, ILC2-deficient mice do not mount an appropriate immune and epithelial type 2 response, resulting in a profound defect in worm expulsion and a non-protective type 3 immune response. In total, our data establish non-redundant functions for ILC2s in the presence of adaptive immune cells at steady state and during disease and argue for a multilayered organization of the immune system on the basis of a spatiotemporal division of labour.

Date: 2022
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DOI: 10.1038/s41586-022-05395-5

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