Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines.
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ICR Authors
Authors
Cano-Gamez, E
Soskic, B
Roumeliotis, TI
So, E
Smyth, DJ
Baldrighi, M
Willé, D
Nakic, N
Esparza-Gordillo, J
Larminie, CGC
Bronson, PG
Tough, DF
Rowan, WC
Choudhary, JS
Trynka, G
Soskic, B
Roumeliotis, TI
So, E
Smyth, DJ
Baldrighi, M
Willé, D
Nakic, N
Esparza-Gordillo, J
Larminie, CGC
Bronson, PG
Tough, DF
Rowan, WC
Choudhary, JS
Trynka, G
Document Type
Journal Article
Date
2020-04-14
Date Accepted
2020-03-18
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.
Citation
Nature communications, 2020, 11 (1), pp. 1801 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723