title: Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity.
abstract: Upon T cell receptor stimulation, CD4+T helper (Th) lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released uponin vitroT cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared with those released by the other subsets. In particular, miR-146a-5p, miR-150-5p, and miR-21-5p are enriched, whereas miR-106a-5p, miR-155-5p, and miR-19a-3p are depleted in Treg-derived EVs. Thein vitroidentified EV-associated microRNA signature was increased in serum of autoimmune patients with psoriasis and returned to healthy levels upon effective treatment with etanercept, a biological drug targeting the TNF pathway and suppressing inflammation. Moreover, Gene Set Enrichment Analysis showed an over-representation of genes relevant for T cell activation, such as CD40L, IRAK1, IRAK2, STAT1, and c-Myb in the list of validated targets of Treg-derived EV miRNAs. At functional level, Treg-derived (but not Th1/Th17-derived) EVs inhibited CD4+T cell proliferation and suppressed two relevant targets of miR-146a-5p: STAT1 and IRAK2. In conclusion, our work identified the miRNAs specifically released by different human CD4+T cell subsets and started to unveil the potential use of their quantity in human serum to mark the pathological elicitation of these cellsin vivoand their biological effect in cell to cell communication during the adaptive immune response.
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Torri
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Carpi
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bulgheroni
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Crosti
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Moro
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Gruarin
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Riccardo L
authors.initials: RL
authors.lastname: Rossi
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Grazisa
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: the Division of Cancer Biology and Therapeutics, Departments of Surgery, Biomedical Sciences and Pathology and Laboratory Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048.
authors.forename: Dolores
authors.initials: D
authors.lastname: Di Vizio
authors.affiliation: the Laboratorio di Epidemiologia Molecolare e Epigenetica Ambientale, Dipartimento di Scienze Cliniche e di Comunità.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hoxha
authors.affiliation: the Laboratorio di Epidemiologia Molecolare e Epigenetica Ambientale, Dipartimento di Scienze Cliniche e di Comunità.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.affiliation: the Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gagliani
authors.affiliation: the Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Tacchetti
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Paroni
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.affiliation: the Dipartimento di Dermatologia, Fondazione IRCCS_Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Corti
authors.affiliation: the Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti.
authors.forename: Luigia
authors.initials: L
authors.lastname: Venegoni
authors.affiliation: the Dipartimento di Dermatologia, Fondazione IRCCS_Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.|the Dipartimento di Medicina, Università degli Studi di Milano Bicocca, 20126 Milan, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Berti
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.|the Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, and.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
authors.affiliation: the Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Naples, Italy, and giuseppe.matarese@unina.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.affiliation: From the INGM Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy, abrignani@ingm.org.|the DISCCO Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, 20122 Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.affiliation: the IRCCS Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica, 20138 Milan, Italy paola.decandia@multimedica.it.
authors.forename: Paola
authors.initials: P
authors.lastname: de Candia
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002478:Cells, Cultured; D000068800:Etanercept / Q000627:therapeutic use; D000067128:Extracellular Vesicles / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D016176:T-Lymphocyte Subsets
chemical_list: D035683:MicroRNAs; D000068800:Etanercept
keywords: autoimmunity; cell-cell interaction; extracellular vesicles; lymphocyte; microRNA (miRNA)