Autocrine TGF-β1 Drives Tissue-specific Differentiation and Function of Resident NK Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2024 Dec 18

PMID 39692745

Authors

Colin Sparano

Dario Solis-Sayago

Nathan Sebastien 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 Juranic Lisnic

Burkhard Becher

Georg Gasteiger

Annette Oxenius

Sonia Tugues

Affiliations

Soon will be listed here.

Abstract

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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