{"title":"Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells.","authors":"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","doi":"10.1084/jem.20240930","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 3","pages":""},"PeriodicalIF":12.6000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1084/jem.20240930","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
第 1 组先天性淋巴细胞（ILCs）包括 NK 细胞和 ILC1s，它们在保护宿主免受病原体和癌症侵害方面发挥着非多余的作用。尽管 NK 细胞具有循环特性，但它们可以在本体发育过程中在选定的组织中建立驻留，形成一个独特的功能亚群。启动、维持和调节 NK 细胞转化为组织驻留型 NK（trNK）细胞的机制目前还不十分清楚。在这里，我们发现自分泌转化生长因子-β（TGF-β）是发育过程中NK细胞在多个腺体组织中驻留的细胞自主驱动因素。TGF-β的细胞内分泌是维持trNK细胞的持续需要，并与Hobit协同增强细胞毒性功能。虽然自分泌 TGF-β 在肿瘤中是多余的，但我们的研究发现，NK 细胞衍生的 TGF-β 在小鼠巨细胞病毒（MCMV）局部感染期间允许细胞毒性 trNK 细胞扩增，并有助于唾液腺中的病毒控制。总之，我们的研究结果揭示了自分泌 TGF-β1 对 trNK 细胞分化和功能的组织特异性调控，这与抗病毒免疫有关。
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.
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Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field.
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