{'fraction_non_alphanumeric': 0.05214521452145215, 'fraction_numerical': 0.029042904290429043, 'mean_word_length': 5.6784140969163, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Cytotoxic T‐lymphocyte antigen‐4 inhibits GATA‐3 but not T‐bet mRNA expression during T helper cell differentiation

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.