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

Eddie Cano-Gamez, Blagoje Soskic (), Theodoros I. Roumeliotis, Ernest So, Deborah J. Smyth, Marta Baldrighi, David Willé, Nikolina Nakic, Jorge Esparza-Gordillo, Christopher G. C. Larminie, Paola G. Bronson, David F. Tough, Wendy C. Rowan, Jyoti S. Choudhary and Gosia Trynka ()
Additional contact information
Eddie Cano-Gamez: Wellcome Genome Campus
Blagoje Soskic: Wellcome Genome Campus
Theodoros I. Roumeliotis: The Institute of Cancer Research
Ernest So: The Institute of Cancer Research
Deborah J. Smyth: Wellcome Genome Campus
Marta Baldrighi: Wellcome Genome Campus
David Willé: GSK R&D
Nikolina Nakic: GSK R&D
Jorge Esparza-Gordillo: GSK R&D
Christopher G. C. Larminie: GSK R&D
Paola G. Bronson: R&D Translational Biology, Biogen
David F. Tough: GSK R&D
Wendy C. Rowan: GSK R&D
Jyoti S. Choudhary: The Institute of Cancer Research
Gosia Trynka: Wellcome Genome Campus

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15543-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15543-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15543-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().