<p>γδ T cells producing either interleukin-17A (γδ<sup>17</sup> cells) or interferon-γ (γδ<sup>IFN</sup> cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an <i>Il17a</i>-GFP:<i>Ifng</i>-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ<sup>17</sup> cell versus γδ<sup>IFN</sup> cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ<sup>17</sup> cells versus γδ<sup>IFN</sup> cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively. Among the signature genes, we show that the co-receptor CD6 and the signaling protein Themis promote the activation and proliferation of peripheral γδ<sup>IFN</sup> cells in response to T cell antigen receptor stimulation in vitro and to <i>Plasmodium</i> infection in vivo. This resource can help to understand the distinct activities of effector γδ T cell subsets in pathophysiology.</p>

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Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation

  • Daniel Inácio,
  • Tiago Amado,
  • Ana Pamplona,
  • Daniel Sobral,
  • Carolina Cunha,
  • Rita F. Santos,
  • Liliana Oliveira,
  • Nelly Rouquié,
  • Alexandre M. Carmo,
  • Renaud Lesourne,
  • Anita Q. Gomes,
  • Bruno Silva-Santos

摘要

γδ T cells producing either interleukin-17A (γδ17 cells) or interferon-γ (γδIFN cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ17 cell versus γδIFN cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ17 cells versus γδIFN cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively. Among the signature genes, we show that the co-receptor CD6 and the signaling protein Themis promote the activation and proliferation of peripheral γδIFN cells in response to T cell antigen receptor stimulation in vitro and to Plasmodium infection in vivo. This resource can help to understand the distinct activities of effector γδ T cell subsets in pathophysiology.