Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells
Group 1 innate lymphoid cells (ILCs) encompass NK cells and ILC1s, which have non-redundant roles in host protection against pathogens and cancer. Despite their circulating nature, NK cells can establish residency in selected tissues during ontogeny, forming a distinct functional subset. The mechanisms that initiate, maintain, and regulate the conversion of NK cells into tissue-resident NK (trNK) cells are currently not well understood. Here, we identify autocrine transforming growth factor-β (TGF-β) as a cell-autonomous driver for NK cell tissue residency across multiple glandular tissues during development. Cell-intrinsic production of TGF-β was continuously required for the maintenance of trNK cells and synergized with Hobit to enhance cytotoxic function. Whereas autocrine TGF-β was redundant in tumors, our study revealed that NK cell-derived TGF-β allowed the expansion of cytotoxic trNK cells during local infection with murine cytomegalovirus (MCMV) and contributed to viral control in the salivary gland. Collectively, our findings reveal tissue-specific regulation of trNK cell differentiation and function by autocrine TGF-β1, which is relevant for antiviral immunity.
Authors
- Caroline Mussak (ORCID: https://orcid.org/0000-0002-1448-1410)
- Annette Oxenius (ORCID: https://orcid.org/0000-0002-2079-2354)
- Georg Gasteiger (ORCID: https://orcid.org/0000-0001-6986-127X)
- Marijne Vermeer (ORCID: https://orcid.org/0000-0001-5869-0532)
- Darío Solís-Sayago (ORCID: https://orcid.org/0000-0002-9574-9107)
- Vanda Juranić Lisnić (ORCID: https://orcid.org/0000-0002-7182-8927)
- Melanie Greter (ORCID: https://orcid.org/0000-0002-7220-5369)
- Gioana Litscher
- Sònia Tugues (ORCID: https://orcid.org/0000-0003-1206-3386)
- Nathan Zangger (ORCID: https://orcid.org/0000-0003-1130-1899)
- Colin Sparano (ORCID: https://orcid.org/0000-0003-0776-6896)
- Hannah Van Hove (ORCID: https://orcid.org/0000-0002-0412-6474)
- Burkhard Becher (ORCID: https://orcid.org/0000-0002-1541-7867)
- Christin Friedrich (ORCID: https://orcid.org/0000-0003-1866-254X)
- Mitchell Bijnen (ORCID: https://orcid.org/0000-0003-2781-8702)
- Lukas Rindlisbacher (ORCID: https://orcid.org/0000-0002-9408-1336)
- Yishu Xu (ORCID: https://orcid.org/0009-0002-6633-5711)
- Frederike Westermann (ORCID: https://orcid.org/0000-0002-3253-2322)
- Stanislav Dergun (ORCID: https://orcid.org/0009-0000-7201-9032)
- Elisa Rallo
Institutions
- University of Rijeka (HR)
- University of Zurich (CH)
- Heidelberg University (DE)
- University of Würzburg (DE)
- University Hospital Heidelberg (DE)
- ETH Zurich (CH)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1084/jem.20240930
- Citations
- 23
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 5.53
Funders
- National Science Foundation
- Novartis Foundation
- Wilhelm Sander-Stiftung
- Institut National de la Santé et de la Recherche Médicale
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Universiteit van Amsterdam
- Eidgenössische Technische Hochschule Zürich
- Centre National de la Recherche Scientifique
- Universität Zürich
- Vontobel-Stiftung
- Olga Mayenfisch Stiftung
- Swiss Cancer Research Foundation
- Washington University School of Medicine in St. Louis