SUMMARY
Innate lymphoid cells (ILCs) are critical in innate immune responses to pathogens and lymphoid organ development. IL-7Rα + ILC subsets, similar to CD4+T helper (Th) cell subsets, produce distinct sets of effector cytokines. However, the molecular control of IL-7Rα + ILC development and maintenance is unclear. Here we report that GATA3 was indispensable for the development of all IL-7Rα + ILC subsets in addition to T cells, but not required for the development of classical NK cells. Gata3 conditional deficient mice had no lymph nodes and were susceptible to Citrobactor rodentium infection. After the ILCs have fully developed, GATA3 remained important for the maintenance and functions of ILC2s. Genome-wide gene expression analyses indicated that GATA3 regulated a similar set of cytokines and receptors in Th2 cells and ILC2s, but not in ILC3s. Thus, GATA3 plays parallel roles in regulating the development and functions of CD4+ T cells and IL-7Rα + ILCs.
Although lincRNAs are implicated in gene regulation in various tissues, little is known about lincRNA transcriptomes in the T cell lineages. Here we identify 1,524 lincRNA clusters in 42 T cell samples from early T cell progenitors to terminally differentiated T helper (TH) subsets. Our analysis revealed highly dynamic and cell-specific expression patterns of lincRNAs during T cell differentiation. Importantly, these lincRNAs are located in genomic regions enriched for protein-coding genes with immune-regulatory functions. Many of them are bound and regulated by the key T cell transcription factors T-bet, GATA-3, STAT4 and STAT6. We demonstrate that the lincRNA LincR-Ccr2-5′AS, together with GATA-3, is an essential component of a regulatory circuit in TH2-specific gene expression and important for TH2 cell migration.
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