title: Th22 cells are expanded in multiple sclerosis and are resistant to IFN-β.
abstract: Th1 and Th17 cells have been considered as effectors in mouse EAE and in the human counterpart, MS. Recently, IL-22, a Th17-related, proinflammatory cytokine, has been associated with a new Th cell subset, defined as Th22, involved in chronic inflammatory conditions, such as psoriasis; the role of IL-22 in MS has not yet been elucidated. Here, we report that similar to Th17 cells, the number of Th22 cells increased in the PB and the CSF of RR MS patients, especially during the active phases of the disease. However, as opposed to Th17 cells, the expansion of Th22 cells occurred before the active phases of the disease. Th22 cells were found to be specific for the autoantigen MBP and also expressed high levels of CCR6 and T-bet, as for Th17 cells, indicating that Th22 self-reactive cells could have CNS-homing properties and be pathogenic in active RRMS patients. Conversely to Th17 cells, Th22 cells displayed lower levels of IFNAR1 and were insensitive to IFN-β inhibition. These data suggest that expansion of Th22 cells in MS could be one of the factors that critically influence resistance to IFN-β therapy.
authors.affiliation: Center for Experimental Research and Medical Studies, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy; Department of Molecular Biotechnology and Health Sciences, Turin, Italy; Department of Clinical and Biological Sciences.
authors.forename: Simona
authors.initials: S
authors.lastname: Rolla
authors.affiliation: Center for Experimental Research and Medical Studies, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy; Department of Molecular Biotechnology and Health Sciences, Turin, Italy; Department of Clinical and Biological Sciences.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bardina
authors.affiliation: Divisions of Neurology and.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Mercanti
authors.affiliation: Department of Medical Sciences, Dermatologic Clinic, University of Turin, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.affiliation: Department of Clinical and Experimental Medicine, Second University of Naples, Italy; and.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Palma
authors.affiliation: Radiology, San Luigi Gonzaga School of Medicine, Orbassano, Italy;
authors.forename: Dario
authors.initials: D
authors.lastname: Gned
authors.affiliation: Human Genetics Foundation, Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Brusa
authors.affiliation: Divisions of Neurology and.
authors.forename: Luca
authors.initials: L
authors.lastname: Durelli
authors.affiliation: Center for Experimental Research and Medical Studies, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy; Department of Molecular Biotechnology and Health Sciences, Turin, Italy; Department of Clinical and Biological Sciences, franco.novelli@unito.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Divisions of Neurology and.
authors.forename: Marinella
authors.initials: M
authors.lastname: Clerico
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D059425:Interferon-gamma Release Tests; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D061251:Primary Cell Culture; D054399:Receptors, CCR6 / Q000096:biosynthesis / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000235:genetics; D020825:T-Box Domain Proteins / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D058504:Th17 Cells / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*; D055815:Young Adult; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor
chemical_list: D001324:Autoantigens; D016899:Interferon-beta; D007378:Interleukins; D004676:Myelin Basic Protein; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor; C106311:CCR6 protein, human
keywords: CD4 T helper cells; autoimmunity; cytokines; human; interferon receptors; interferons