Systems analysis of human T helper17 cell differentiation uncovers distinct time-regulated transcriptional modules

Alessia Capone, Chiara Naro, Manuela Bianco, Marco De Bardi, Floriane Noël, Paolo Macchi, Luca Battistini, Vassili Soumelis, Elisabetta Volpe, Claudio Sette

Research output: Contribution to journalArticlepeer-review

Abstract

T helper (Th) 17 cells protect from infections and are pathogenic in autoimmunity. While human Th17 cell differentiation has been defined, the global and stepwise transcriptional changes accompanying this process remain uncharacterized. Herein, by performing transcriptome analysis of human Th17 cells, we uncovered three time-regulated modules: early, involving exclusively “signaling pathways” genes; late, characterized by response to infections; and persistent, involving effector immune functions. To assign them an inflammatory or regulatory potential, we compared Th17 cells differentiated in presence or absence of interleukin (IL)-1β, respectively. Most inflammatory genes belong to the persistent module, whereas regulatory genes are lately or persistently induced. Among inflammatory genes, we identified the effector molecules IL17A, IL17F, IL26, IL6, interferon (IFN)G, IFNK, LTA, IL1A, platelet-derived growth factor (PDGF) A and the transcriptional regulators homeodomain-only protein homeobox (HOPX) and sex-determining-region-Y-box (SOX)2, whose expression was independently validated. This study provides an integrative representation of the stepwise human Th17 differentiation program and offers new perspectives toward therapeutic targeting of Th17-related autoimmune diseases.

Original languageEnglish
Article number102492
JournaliScience
Volume24
Issue number5
DOIs
Publication statusPublished - May 21 2021

Keywords

  • Immunology
  • Omics
  • Systems Biology

ASJC Scopus subject areas

  • General

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