STAT3 signaling induces the differentiation of human ICOS(+) CD4 T cells helping B lymphocytes.
The generation of high-affinity antibodies and the development of B cell memory are dependent on the help provided by CD4 T cells. Mouse studies indicate that STAT3 signaling in CD4 T cells promotes the acquisition of the B cell help function. However, the role of STAT3 in humans has been controversial. In this study, we show that IL-6 and other STAT3 activating cytokines (IL-21 and IL-27) induce the differentiation of CD4 T cells promoting antibody production by B cells. The acquisition of B cell stimulating properties by naive cord blood CD4 T cells required the STAT3-dependent expression of ICOS and IL-21. Gene reporter and ChIP experiments unambiguously demonstrated that upon IL-6 stimulation, STAT3 induces the transcription of the ICOS gene through direct recruitment to the proximal promoter region indicating that STAT3 acts in part through the direct activation of the ICOS gene.
Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Charleroi, Belgium.
Laure
L
Ysebrant de Lendonck
Fouad
F
Eddahri
Yves
Y
Delmarcelle
Muriel
M
Nguyen
Oberdan
O
Leo
Stanislas
S
Goriely
Arnaud
A
Marchant
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D064094:Interleukin-27 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D050796:STAT3 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction; D015533:Transcriptional Activation
C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D064094:Interleukin-27; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D018664:Interleukin-12