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- Title
Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines.
- Authors
Cano-Gamez, Eddie; Soskic, Blagoje; Roumeliotis, Theodoros I.; So, Ernest; Smyth, Deborah J.; Baldrighi, Marta; Willé, David; Nakic, Nikolina; Esparza-Gordillo, Jorge; Larminie, Christopher G. C.; Bronson, Paola G.; Tough, David F.; Rowan, Wendy C.; Choudhary, Jyoti S.; Trynka, Gosia
- Abstract
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. Cytokines critically control the differentiation and functions of activated naïve and memory T cells. Here the authors show, using multi-omics and single-cell analyses, that naïve and memory T cells exhibit distinct cytokine responses, in which an 'effectorness gradient' is depicted by a transcriptional continuum, which shapes the downstream genetic programs.
- Subjects
IMMUNE response
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-15543-y