| Title | Cytotoxic T-lymphocyte antigen-4 inhibits GATA-3 but not T-bet mRNA expression during T helper cell differentiation |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2006 |
| Authors | Nasta, F., Ubaldi V., Pace L., Doria G., and Pioli Claudio |
| Journal | Immunology |
| Volume | 117 |
| Pagination | 358-367 |
| ISSN | 00192805 |
| Keywords | animal cell, Animals, Antigens, article, CD, CD28 antigen, CD3 antigen, CD4+ T lymphocyte, cell differentiation, Cell Polarity, cell stimulation, Cell Surface, controlled study, cytokine, cytotoxic T lymphocyte, cytotoxic T lymphocyte antigen 4, Differentiation, GATA3 Transcription Factor, gene expression regulation, helper cell, Helper-Inducer, Inbred C57BL, interleukin 4, interleukin 4 receptor alpha, Messenger, messenger RNA, Mice, mouse, nonhuman, Polarization, priority journal, protein expression, Receptors, regulatory mechanism, Reverse Transcriptase Polymerase Chain Reaction, RNA, STAT6 protein, STAT6 Transcription Factor, T-Box Domain Proteins, T-Lymphocytes, Th1 cell, Th1 Cells, Th2 cell, Th2 Cells, transcription factor GATA 3, transcription factor T bet, Transcription Factors, upregulation |
| Abstract | Naive CD4+ T-cell differentiation to T helper 1 (Th1) and Th2 cells is dependent on T-bet and GATA-3 factors, respectively. T-bet and GATA-3, indeed, through chromatin remodelling allow transcriptional activation of Ifnγ and Th2 cytokine (Il4, Il5, Il13) genes, respectively. We investigated the effects of the negative costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) on GATA-3 and T-bet mRNA expression and Th cell differentiation in mouse naive CD4+ T cells. Our results show that CTLA-4 inhibits GATA-3 mRNA expression and Th2 cell differentiation. At variance, CTLA-4 does not affect T-bet mRNA expression and Th1 cell differentiation. GATA-3 mRNA expression is inhibited when CD4+ cells are stimulated under both neutral (i.e. absence of cytokines) and Th2-polarizing (i.e. presence of interleukin (IL)-4) conditions, the effect being larger under the latter condition. Hence CTLA-4 might affect the IL-4/signal transducer and activator of transcription-6 (STAT6) pathway leading to GATA-3 mRNA up-regulation. We found, indeed, that CTLA-4 engagement inhibits STAT6 activation leaving unaffected the STAT6 protein level. Moreover, CTLA-4 engagement drastically inhibits IL-4Rα mRNA and protein up-regulation under Th2-polarizing conditions. Thus, CTLA-4 exerts a tight control on Th2 cell differentiation by negatively regulating both the CD3/CD28 and the IL-4/STAT6 pathways. © 2005 Blackwell Publishing Ltd. |
| Notes | cited By 19 |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-33645063722&doi=10.1111%2fj.1365-2567.2005.02309.x&partnerID=40&md5=5a6e4b76a12f94a5a6a3f43b2bdaa4a3 |
| DOI | 10.1111/j.1365-2567.2005.02309.x |
| Citation Key | Nasta2006358 |
