Research Topic

TGF-β as a Key Regulator of NK and ILCs Development and Functions

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TGF‐β, belonging to TGF‐β superfamily, emerged during the evolution of multicellular organisms, pointing out the relevance of this cytokine in the increasing diversity and complexity characterizing metazoans’ development. In mammals, TGF‐β is involved in the homeostatic regulation of haematopoietic and ...

TGF‐β, belonging to TGF‐β superfamily, emerged during the evolution of multicellular organisms, pointing out the relevance of this cytokine in the increasing diversity and complexity characterizing metazoans’ development. In mammals, TGF‐β is involved in the homeostatic regulation of haematopoietic and non-haematopoietic tissues and shows the interesting capability of regulating the development of innate lymphoid cells (ILCs). The ILC family includes different subtypes that originate from a common innate lymphoid precursor (CILP) and are characterized by different transcription factors signatures, tissue distribution and functions. TGF-β favors the differentiation of helper members of the ILC family such as ILC1 or regulatory innate lymphoid cells (ILCreg). On the contrary, it negatively impacts on the differentiation of Natural Killer (NK) cells favoring the onset of cells with a poor cytolytic decidual‐like phenotype. Thus, TGF-β can limit the innate immune surveillance in cancer and viral infections through the dysregulation of the normal NK/ILC1 differentiation ratio and/or the enrichment of regulatory effectors. These mechanisms join the ability of TGF-β to hamper the main effector functions of NK cells by reducing the surface expression of crucial activating receptors such as NKp30 and NKG2D and inhibiting the metabolic mTOR pathway. Moreover, TGF-β impacts on the NK migratory properties since it profoundly modifies their chemokine receptor repertoire. Importantly, other cytokines can either weaken or reinforce the immunoregulatory functions of TGF-β, as recently demonstrated for IL-18. This Research Topic aims to collect Original Research articles as well as Review, Mini Review, Perspective or Commentary articles highlighting recent advances or providing new information about the TGF-β-mediated regulation of ILCs compartment in human and mouse.


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