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STAT3 signaling induces the differentiation of human ICOS(+) CD4 T cells helping B lymphocytes.
oleh: Laure Ysebrant de Lendonck, Fouad Eddahri, Yves Delmarcelle, Muriel Nguyen, Oberdan Leo, Stanislas Goriely, Arnaud Marchant
Format: | Article |
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Diterbitkan: | Public Library of Science (PLoS) 2013-01-01 |
Deskripsi
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.