Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines.
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Date
2020-04-14Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
CD4-Positive T-Lymphocytes
Humans
Receptors, Antigen, T-Cell
Proteome
Cytokines
Lymphocyte Activation
Cell Polarity
Gene Expression Regulation
Principal Component Analysis
Middle Aged
Male
Single-Cell Analysis
Transcriptome
CD28 Antigens
Language
eng
Date accepted
2020-03-18
License start date
2020-04-14
Citation
Nature communications, 2020, 11 (1), pp. 1801 - ?
Publisher
NATURE RESEARCH