ERK phosphorylation and miR-181a expression modulate activation of human memory T(H)17 cells

作者：Mele Federico; Basso Camilla; Leoni Cristina; Aschenbrenner Dominik; Becattini Simone; Latorre Daniela; Lanzavecchia Antonio; Sallusto Federica^*; Monticelli Silvia

来源：Nature Communications, 2015, 6(1): 6431.

DOI：10.1038/ncomms7431

T helper (T-H) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory T-H cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the T(H)17, but not T(H)1 or T(H)2 subset. In human memory T(H)17 cells, miR-181a regulates responses to cognate antigens through modulation of ERK phosphorylation. By enhancing the signalling cascade from the T-cell receptor, such molecular network reduces the threshold of T(H)17 cell activation. Moreover, at a late time point, the same network induces a self-regulatory mechanism dependent on ID3, a negative regulator of transcription factors that control RORC expression, thus modulating T(H)17 activity. Our results demonstrate that the phenotype acquired by T-H cells during priming contributes to their threshold of activation to secondary antigenic stimulations, thus influencing memory responses.

• 出版日期2015-3