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The transcription factor GATA3 is critical for the development of all IL-7Ra-expressing innate lymphoid cells (ILCs) and maintenance of type 2 ILCs

ABSTRACT: Innate lymphoid cells (ILCs) play critical roles during innate immune responses to pathogens and lymphoid organ development. IL-7Ra+ ILC subsets, similar to T helper (Th) cell subsets, produce distinctive effector cytokines. The molecular control of IL-7Ra+ ILC development and maintenance has yet to be dissected. Here we report that GATA3 is indispensable for the development of all IL-7Ra+ ILC subsets and T cells. Gata3 conditional deficient mice have no lymph nodes and are susceptible to Citrobactor rodentium infection. Genome-wide gene analyses indicate that GATA3 regulates similar set of cytokines and receptors in ILC2s and Th2 cells and is critical for the maintenance of ILC2s. Thus, GATA3 plays parallel roles in establishing and regulating both adaptive and innate lymphocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE47851 | GEO | 2014/03/13

SECONDARY ACCESSION(S): PRJNA208082

REPOSITORIES: GEO

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The transcription factor GATA3 is critical for the development of all IL-7Ra-expressing innate lymphoid cells (ILCs) and maintenance of type 2 ILCs

Project description:Innate lymphoid cells (ILCs) play critical roles during innate immune responses to pathogens and lymphoid organ development. IL-7Ra+ ILC subsets, similar to T helper (Th) cell subsets, produce distinctive effector cytokines. The molecular control of IL-7Ra+ ILC development and maintenance has yet to be dissected. Here we report that GATA3 is indispensable for the development of all IL-7Ra+ ILC subsets and T cells. Gata3 conditional deficient mice have no lymph nodes and are susceptible to Citrobactor rodentium infection. Genome-wide gene analyses indicate that GATA3 regulates similar set of cytokines and receptors in ILC2s and Th2 cells and is critical for the maintenance of ILC2s. Thus, GATA3 plays parallel roles in establishing and regulating both adaptive and innate lymphocytes. To identify GATA3 regulated genes in type 2 innate lymphoid cells by tamoxifen-mediated acute deletion of Gata3 gene.

2014-03-13 | E-GEOD-47851 | biostudies-arrayexpress

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Project description:GATA3 is indispensable for the development of all IL-7RÎ±-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7RÎ± expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and RORÎ³t. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets. To identify GATA3 regulated genes in total ILC3s with RNA-Seq; To identify unique genes expressed by CCR6+ ILC3 or NKp46+ ILC3 and GATA3 regulated genes within these two ILC3 subsets with RNA-Seq; To identify GATA3 direct binding sites in ILC3s, ILC2s and Th2 cells with ChIP-Seq.

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