TY - JOUR
T1 - Systems analysis of human T helper17 cell differentiation uncovers distinct time-regulated transcriptional modules
AU - Capone, Alessia
AU - Naro, Chiara
AU - Bianco, Manuela
AU - De Bardi, Marco
AU - Noël, Floriane
AU - Macchi, Paolo
AU - Battistini, Luca
AU - Soumelis, Vassili
AU - Volpe, Elisabetta
AU - Sette, Claudio
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Immunology
KW - Omics
KW - Systems Biology
KW - Immunology
KW - Omics
KW - Systems Biology
UR - http://hdl.handle.net/10807/189521
U2 - 10.1016/j.isci.2021.102492
DO - 10.1016/j.isci.2021.102492
M3 - Article
SN - 2589-0042
SP - 1
EP - 14
JO - iScience
JF - iScience
ER -
