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Th17 cells have critical roles in mucosal defense and are major contributors to inflammatory disease. Their differentiation requires the nuclear hormone receptor RORγt working with multiple other essential transcription factors (TFs). We have used an iterative systems approach, combining genome-wide TF occupancy, expression profiling of TF mutants, and expression time series to delineate the Th17...
αβ and γδ T cells arise from a common thymocyte progenitor during development in the thymus. Emerging evidence suggests that the pre-T cell receptor (pre-TCR) and γδ T cell receptor (γδTCR) play instructional roles in specifying the αβ and γδ T-lineage fates, respectively. Nevertheless, the signaling pathways differentially engaged to specify fate and promote the development of these lineages remain...
Signals transduced by Notch receptors are indispensable for T cell specification and differentiation of αβ T lineage cells. However, the role of Notch signals during αβ versus γδ T lineage decision remains controversial. Here, we addressed this question by employing a clonal analysis of CD4 − CD8 − (DN) progenitor potential to position the divergence of αβ and γδ T cell lineages to...
In this issue of Immunity, Kersh and colleagues (Xi et al., 2006) investigate the regulatory network that permits two otherwise clashing cellular processes—proliferation and gene rearrangement—to occur at temporally distinct periods following the formation of the pre-T cell receptor (pre-TCR) complex.
The survival of immature T cell precursors is dependent on both thymus-derived extrinsic signals and self-autonomous pre-TCR-mediated signals. While the role of cytokines and the pre-TCR in promoting thymocyte survival has been well established, the relationship between pro- and anti-apoptotic signaling cascades remains poorly defined. Recent studies have established a link between cell survival and...
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