title: Intracellular modulation, extracellular disposal and serum increase of MiR-150 mark lymphocyte activation.
abstract: Activated lymphocytes release nano-sized vesicles (exosomes) containing microRNAs that can be monitored in the bloodstream. We asked whether elicitation of immune responses is followed by release of lymphocyte-specific microRNAs. We found that, upon activation in vitro, human and mouse lymphocytes down-modulate intracellular miR-150 and accumulate it in exosomes. In vivo, miR-150 levels increased significantly in serum of humans immunized with flu vaccines and in mice immunized with ovalbumin, and this increase correlated with elevation of antibody titers. Immunization of immune-deficient mice, lacking MHCII, resulted neither in antibody production nor in elevation of circulating miR-150. This study provides proof of concept that serum microRNAs can be detected, with minimally invasive procedure, as biomarkers of vaccination and more in general of adaptive immune responses. Furthermore, the prompt reduction of intracellular level of miR-150, a key regulator of mRNAs critical for lymphocyte differentiation and functions, linked to its release in the external milieu suggests that the selective extracellular disposal of microRNAs can be a rapid way to regulate gene expression during lymphocyte activation.
authors.affiliation: INGM (Istituto Nazionale Genetica Molecolare), Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: de Candia
authors.forename: Anna
authors.initials: A
authors.lastname: Torri
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gorletta
authors.forename: Maya
authors.initials: M
authors.lastname: Fedeli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bulgheroni
authors.forename: Cristina
authors.initials: C
authors.lastname: Cheroni
authors.forename: Francesco
authors.initials: F
authors.lastname: Marabita
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Crosti
authors.forename: Monica
authors.initials: M
authors.lastname: Moro
authors.forename: Elena
authors.initials: E
authors.lastname: Pariani
authors.forename: Luisa
authors.initials: L
authors.lastname: Romanò
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.forename: Grazisa
authors.initials: G
authors.lastname: Rossetti
authors.forename: Riccardo L
authors.initials: RL
authors.lastname: Rossi
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.forename: Giulia
authors.initials: G
authors.lastname: Casorati
authors.forename: Paolo
authors.initials: P
authors.lastname: Dellabona
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016000:Cluster Analysis; D011992:Endosomes / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D014611:Vaccination
chemical_list: D035683:MicroRNAs; C533097:MIR150, human; C529101:Mirn150 microRNA, mouse