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.
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December 18 2024
Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells
In Special Collection:
Tissue Microenvironment and Immune Memory
Colin Sparano
,
Colin Sparano
*
(Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Visualization, Writing - original draft, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Darío Solís-Sayago
,
Darío Solís-Sayago
*
(Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Visualization, Writing - original draft, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Nathan Sébastien Zangger
,
Nathan Sébastien Zangger
(Data curation, Formal analysis, Investigation, Resources)
3
Institute of Microbiology, ETH Zürich
, Zürich, Switzerland
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Lukas Rindlisbacher
,
Lukas Rindlisbacher
(Investigation, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Hannah Van Hove
,
Hannah Van Hove
(Investigation)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Marijne Vermeer
,
Marijne Vermeer
(Investigation, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Frederike Westermann
,
Frederike Westermann
(Investigation, Resources)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Caroline Mussak
,
Caroline Mussak
(Investigation)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Elisa Rallo
,
Elisa Rallo
(Investigation)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Stanislav Dergun
,
Stanislav Dergun
(Investigation)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Gioana Litscher
,
Gioana Litscher
(Investigation, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Yishu Xu
,
Yishu Xu
(Investigation)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Mitchell Bijnen
,
Mitchell Bijnen
(Investigation, Methodology, Resources, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Christin Friedrich
,
Christin Friedrich
(Writing - review & editing)
5
Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg
, Würzburg, Germany
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Melanie Greter
,
Melanie Greter
(Conceptualization)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Vanda Juranić Lisnić
,
Vanda Juranić Lisnić
(Methodology)
4
Center for Proteomics, Faculty of Medicine, University of Rijeka
, Rijeka, Croatia
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Burkhard Becher
,
Burkhard Becher
(Funding acquisition, Resources, Supervision, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
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Georg Gasteiger
,
Georg Gasteiger
(Conceptualization, Resources, Writing - review & editing)
5
Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg
, Würzburg, Germany
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Annette Oxenius
,
Annette Oxenius
(Resources, Supervision)
3
Institute of Microbiology, ETH Zürich
, Zürich, Switzerland
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Sonia Tugues
(Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing)
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
2Department of Immunology, Medical Faculty Mannheim,
Mannheim Institute for Innate Immunosciences (MI3), Heidelberg University
, Heidelberg, Germany
Correspondence to Sonia Tugues: [email protected]
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Colin Sparano
Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Visualization, Writing - original draft, Writing - review & editing
*
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Darío Solís-Sayago
Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Visualization, Writing - original draft, Writing - review & editing
*
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Nathan Sébastien Zangger
Data curation, Formal analysis, Investigation, Resources
3
Institute of Microbiology, ETH Zürich
, Zürich, Switzerland
Lukas Rindlisbacher
Investigation, Writing - review & editing
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Hannah Van Hove
Investigation
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Marijne Vermeer
Investigation, Writing - review & editing
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Frederike Westermann
Investigation, Resources
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Caroline Mussak
Investigation
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Elisa Rallo
Investigation
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Stanislav Dergun
Investigation
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Gioana Litscher
Investigation, Writing - review & editing
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Yishu Xu
Investigation
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Mitchell Bijnen
Investigation, Methodology, Resources, Writing - review & editing
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Christin Friedrich
Writing - review & editing
5
Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg
, Würzburg, Germany
Melanie Greter
Conceptualization
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Vanda Juranić Lisnić
Methodology
4
Center for Proteomics, Faculty of Medicine, University of Rijeka
, Rijeka, Croatia
Burkhard Becher
Funding acquisition, Resources, Supervision, Writing - review & editing
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
Georg Gasteiger
Conceptualization, Resources, Writing - review & editing
5
Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg
, Würzburg, Germany
Annette Oxenius
Resources, Supervision
3
Institute of Microbiology, ETH Zürich
, Zürich, Switzerland
Sonia Tugues
Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
1
Institute of Experimental Immunology, University of Zürich
, Zürich, Switzerland
2Department of Immunology, Medical Faculty Mannheim,
Mannheim Institute for Innate Immunosciences (MI3), Heidelberg University
, Heidelberg, Germany
Correspondence to Sonia Tugues: [email protected]
*
C. Sparano and D. Solís-Sayago contributed equally to this paper.
Disclosures: The authors declare no competing interests exist.
Received:
May 29 2024
Revision Received:
October 21 2024
Accepted:
November 20 2024
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funder(s):
Swiss National Science Foundation
- Award Id(s): PR00P3_179775
Funder(s):
Swiss Cancer Research Foundation
- Award Id(s): KFS-5420-02-2021
Funder(s):
Universität Zürich Candoc
- Award Id(s): K-41311-01-01
Funder(s):
Sassella Foundation
Funder(s):
Vontobel Foundation
Funder(s):
Novartis Foundation
Funder(s):
Olga Mayenfisch Stiftung
Funder(s):
Wilhelm Sander-Stiftung
© 2024 Sparano et al.
2024
Sparano et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
This work is licensed under a
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
.
J Exp Med (2025) 222 (3): e20240930.
Article history
Received:
May 29 2024
Revision Received:
October 21 2024
Accepted:
November 20 2024
Connected Content
Citation
Colin Sparano, Darío Solís-Sayago, Nathan Sébastien Zangger, Lukas Rindlisbacher, Hannah Van Hove, Marijne Vermeer, Frederike Westermann, Caroline Mussak, Elisa Rallo, Stanislav Dergun, Gioana Litscher, Yishu Xu, Mitchell Bijnen, Christin Friedrich, Melanie Greter, Vanda Juranić Lisnić, Burkhard Becher, Georg Gasteiger, Annette Oxenius, Sonia Tugues; Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells. J Exp Med 3 March 2025; 222 (3): e20240930. doi: https://doi.org/10.1084/jem.20240930
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