title: ERK phosphorylation and miR-181a expression modulate activation of human memory TH17 cells.
abstract: 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.
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Mele
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Camilla
authors.initials: C
authors.lastname: Basso
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Leoni
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Aschenbrenner
authors.affiliation: 1] Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland [2] Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Becattini
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Latorre
authors.affiliation: 1] Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland [2] Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Monticelli
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D002176:Candida albicans / Q000378:metabolism; D002454:Cell Differentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction; D058504:Th17 Cells / Q000166:cytology*
chemical_list: D000941:Antigens; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C529100:mirn181 microRNA, mouse; D048049:Extracellular Signal-Regulated MAP Kinases