Transforming growth factor-β and Notch ligands act as opposing environmental cues in the plasticity of type 3 innate lymphoid cells
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ABSTRACT: Group 3 innate lymphoid cells (ILC3) are composed of NCR- and NCR+ subsets located at mucosal sites exposed to billions of commensal microbes and potentially harmful pathogens. Together with T cells, the various ILC3 subsets maintain the balance between homeostasis and immune activation. Using genetic mapping, we reveal here the existence of a new subset of NCR- ILC3 transiently expressing Ncr1 but strongly related to unlabeled NCR- ILC3, demonstrating previously unsuspected heterogeneity within the NCR- ILC3 population. Notch signaling is required for the differentiation of NCR- ILC3 into NCR+ ILC3. However, we show here that Notch signaling must be sustained for the maintenance of the NCR+ phenotype and that TGF-β impairs the development of NCR+ ILC3. Thus, ILC3 diversity and the plasticity of the NCR- and NCR+ subsets is regulated by the balance between the opposing effects of Notch and TGF-β signaling, maintaining homeostasis in the face of continual challenges.
ORGANISM(S): Mus musculus
PROVIDER: GSE79410 | GEO | 2016/06/01
SECONDARY ACCESSION(S): PRJNA315770
REPOSITORIES: GEO
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