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Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines

Autori:

  • Cano-Gamez E.,
  • Soskic B.,
  • Roumeliotis T. I.,
  • So E.,
  • Smyth D. J.,
  • Baldrighi M.,
  • Willé D.,
  • Nakic N.,
  • Esparza-Gordillo, J.,
  • Larminie C. G. C.,
  • Bronson P. G.,
  • Tough D. F.,
  • Rowan W. C.,
  • Choudhary J. S.,
  • Trynka G.

Sommario:

Naïve CD4+ T cells coordinate the immune response by acquiring an effector phenotype in response to cytokines. However, the cytokine responses in memory T cells remain largely understudied. Here we use quantitative proteomics, bulk RNA-seq, and single-cell RNA-seq of over 40,000 human naïve and memory CD4+ T cells to show that responses to cytokines differ substantially between these cell types. Memory T cells are unable to differentiate into the Th2 phenotype, and acquire a Th17-like phenotype in response to iTreg polarization. Single-cell analyses show that T cells constitute a transcriptional continuum that progresses from naïve to central and effector memory T cells, forming an effectorness gradient accompanied by an increase in the expression of chemokines and cytokines. Finally, we show that T cell activation and cytokine responses are influenced by the effectorness gradient. Our results illustrate the heterogeneity of T cell responses, furthering our understanding of inflammation.

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