Abstract
Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells and are a major source of innate TH2 cytokine secretion upon allergen exposure or parasitic-worm infection. Accumulating studies have revealed that transcription factors, including GATA-3, Bcl11b, Gfi1, RORα, and Ets-1, play a role in ILC2 differentiation. Recent reports have further revealed that the characteristics and functions of ILC2 are influenced by the physiological state of the tissues. Specifically, the type of inflammation strongly affects the ILC2 phenotype in tissues. Inhibitory ILC2s, memory-like ILC2s, and ex-ILC2s with ILC1 features acquire their characteristic properties following exposure to their specific inflammatory environment. We have recently reported a new ILC2 population, designated as exhausted-like ILC2s, which emerges after a severe allergic inflammation. Exhausted-like ILC2s are featured with low reactivity and high expression of inhibitory receptors. Therefore, for a more comprehensive understanding of ILC2 function and differentiation, we review the recent knowledge of transcriptional regulation of ILC2 differentiation and discuss the roles of the Runx transcription factor in controlling the emergence of exhausted-like ILC2s. The concept of exhausted-like ILC2s sheds a light on a new aspect of ILC2 biology in allergic diseases.
Highlights
Innate lymphoid cells (ILCs) are lymphocytes responsible for innate cytotoxicity or helper functions [1,2,3]
ILC2s are characterized by the production of the TH2 cytokines interleukin 4 (IL-4), IL-5, IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
Previous studies demonstrated the importance of transcription factors, such as GATA binding protein 3 (GATA-3), B-Cell lymphoma/leukaemia 11B (Bcl11b), growth factor independent 1 transcription repressor (Gfi-1), RAR related orphan receptor A (RORα), and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1), for ILC2 differentiation [7,15,39,40,41,42,43,44,45,46]
Summary
Innate lymphoid cells (ILCs) are lymphocytes responsible for innate cytotoxicity or helper functions [1,2,3]. ILC2s are characterized by the production of the TH2 cytokines interleukin 4 (IL-4), IL-5, IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) All of these expressions are positively regulated by the transcription factor GATA binding protein 3 (GATA-3) [15]. Previous studies demonstrated the importance of transcription factors, such as GATA-3, B-Cell lymphoma/leukaemia 11B (Bcl11b), growth factor independent 1 transcription repressor (Gfi-1), RAR related orphan receptor A (RORα), and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1), for ILC2 differentiation [7,15,39,40,41,42,43,44,45,46]. It remains to be elucidated how Ets-1 regulates the ILC2 fitness and function
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