ERK phosphorylation and miR-181a expression modulate activation of human memory TH17 cells

Mele, Federico; Basso, Camilla; Leoni, Cristina; Aschenbrenner, Dominik; Becattini, Simone; Latorre, Daniela; Lanzavecchia, Antonio; Sallusto, Federica; Monticelli, Silvia

doi:10.1038/ncomms7431

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Journal article

ERK phosphorylation and miR-181a expression modulate activation of human memory TH17 cells

Mele, Federico Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Basso, Camilla Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Leoni, Cristina Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Aschenbrenner, Dominik Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Becattini, Simone Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, ETH Zurich, Zurich, Switzerland
Latorre, Daniela Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, ETH Zurich, Zurich, Switzerland
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Monticelli, Silvia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland

16.03.2015

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Nature communications. - 2015, vol. 6, p. 6431

English T helper (TH) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory TH cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the TH17, but not TH1 or TH2 subset. In human memory TH17 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 TH17 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 TH17 activity. Our results demonstrate that the phenotype acquired by TH cells during priming contributes to their threshold of activation to secondary antigenic stimulations, thus influencing memory responses.

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