title: iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles.
abstract: BACKGROUND
  Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes.
  
  
  OBJECTIVE
  To identify possible changes in the phenotype of iNKT cells in patients with different clinical forms of MS and find alterations in their polyfunctionality [i.e., ability to produce simultaneously up to four cytokines such as IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-4].
  
  
  METHODS
  We studied a total of 165 patients, 91 with a relapsing-remitting form [RR; 31 were treated with interferon (IFN)1a-β, 25 with natalizumab (NAT), 29 with glatiramer acetate; 17 were newly diagnosed RR without treatment, 19 not-active RR without treatment]. Forty-four patients had a progressive MS: 20 primary progressive (PP) and 24 secondary progressive (SP). A total of 55 age- and sex-matched subjects represented healthy controls (CTR). Among fresh peripheral blood mononuclear cells, iNKT cells were identified by flow cytometry. Moreover, the capability of iNKT cells to produce different cytokines (IL-17, TNF-α, IFN-γ, and IL-4) afterin vitrostimulation were evaluated in 18 RR (11 treated with NAT and 7 with IFN), 4 PP, 6 SP, and 16 CTR.
  
  
  RESULTS
  No main differences were found in iNKT cell phenotype among MS patients with different MS forms or during different treatments. However, the polyfunctional response of iNKT cells showed Th1 and Th17 profiles. This was well evident in patients with SP form, who are characterized by high levels of inflammation and neurodegeneration, and exhibited a sustained increase in the production of Th17 cytokines. Patients treated with NAT displayed lower levels of iNKT cells producing IL-17, TNF-α, and IFN-γ.
  
  
  CONCLUSIONS
  Our data suggest that the progressive phase of the disease is characterized by permanent iNKT activation and a skewing towards an inflammatory phenotype. Compared to other treatments, NAT was able to modulate iNKT cell function.
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: De Biasi
authors.affiliation: Neurology Unit, Department of Biomedical, Metabolic and Neurosciences, Nuovo Ospedale Civile Sant'Agostino Estense, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Simone
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bianchini
authors.affiliation: Neurology Unit, Department of Biomedical, Metabolic and Neurosciences, Nuovo Ospedale Civile Sant'Agostino Estense, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Ferraro
authors.affiliation: Neurology Unit, Department of Biomedical, Metabolic and Neurosciences, Nuovo Ospedale Civile Sant'Agostino Estense, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vitetta
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Gibellini
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.affiliation: Neurology Unit, Department of Biomedical, Metabolic and Neurosciences, Nuovo Ospedale Civile Sant'Agostino Estense, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sola
authors.affiliation: Department of Medical and Surgical Sciences of Children and Adults, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
keywords: cytokines; flow cytometry; iNKT cells; immunomodulatory drugs; multiple sclerosis