title: Divergent effects of type-I interferons on regulatory T cells.
abstract: Regulatory T cells (Treg) exert a dominant role in the protection of unwanted immune responses and in the resolution of inflammation. To ensure the proper mounting of protective immune responses, Treg should be finely modulated by microenvironmental signals, mostly conveyed by cytokines. Type-I interferons are pleiotropic cytokines, best known for their anti-viral activities but also playing relevant immunostimulatory as well as immunomodulatory functions. The impact of type-I interferons on Treg homeostasis and functions is quite controversial, as some studies indicate that interferons sustain Treg stability and suppression, while other reports describe a null or even negative role for interferons in Treg activities. Interferons may also establish alternative routes of suppression, through the induction of other suppressive populations, such as Tr1 and the recently discovered FoxA1+ Treg. Discrepant results about Treg behavior in vivo emerge also from data collected in patients with multiple sclerosis, chronic hepatitis C or cancer undergoing interferon therapy. Concurrent events, such as Treg-extrinsic interferon activities, desensitization to chronic interferon exposure, and changes in microenvironmental signals during the evolution of diseases, may contribute to depict such a complex scenario, in which short-term and long-term effects of interferon exposure may give rise to apparently opposite conclusions.
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Policlinico Umberto I, Viale del Policlinico 155, I-00161 Rome, Italy. Electronic address: silvia.piconese@uniroma1.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Piconese
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Policlinico Umberto I, Viale del Policlinico 155, I-00161 Rome, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Pacella
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Policlinico Umberto I, Viale del Policlinico 155, I-00161 Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Timperi
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Policlinico Umberto I, Viale del Policlinico 155, I-00161 Rome, Italy; Istituto Pasteur - Fondazione Cenci Bolognetti, Viale Regina Elena 291, I-00161 Rome, Italy. Electronic address: vincenzo.barnaba@uniroma1.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
mesh_terms: D016207:Cytokines / Q000276:immunology; D006526:Hepatitis C / Q000628:therapy; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D007249:Inflammation; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D007372:Interferons / Q000276:immunology; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D007372:Interferons
keywords: Immunomodulation; Regulatory T cells; Type-1 Interferons