De Biasi Sara, Simone Anna Maria, Nasi Milena, Bianchini Elena, Ferraro Diana, Vitetta Francesca, Gibellini Lara, Pinti Marcello, Del Giovane Cinzia, Sola Patrizia, Cossarizza Andrea
Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia , Modena , Italy.
Neurology Unit, Department of Biomedical, Metabolic and Neurosciences, Nuovo Ospedale Civile Sant'Agostino Estense, University of Modena and Reggio Emilia , Modena , Italy.
Front Immunol. 2016 Nov 30;7:555. doi: 10.3389/fimmu.2016.00555. eCollection 2016.
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.
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].
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) after stimulation were evaluated in 18 RR (11 treated with NAT and 7 with IFN), 4 PP, 6 SP, and 16 CTR.
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.
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.
多发性硬化症（MS）是一种伴有神经退行性变和炎症的自身免疫性疾病，其特征为不同T细胞亚群的多种改变。然而，关于自然杀伤T（iNKT）淋巴细胞的作用，相关数据较少。
确定不同临床类型MS患者中iNKT细胞表型的可能变化，并发现其多功能性（即同时产生多达四种细胞因子，如白细胞介素（IL）-17、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ和IL-4的能力）的改变。
我们共研究了165例患者，其中91例为复发缓解型[RR；31例接受干扰素（IFN）1a-β治疗，25例接受那他珠单抗（NAT）治疗，29例接受醋酸格拉替雷治疗；17例为新诊断未治疗的RR患者，19例为非活动未治疗的RR患者]。44例患者为进展型MS：20例为原发进展型（PP），24例为继发进展型（SP）。共有55例年龄和性别匹配的受试者作为健康对照（CTR）。在新鲜外周血单个核细胞中，通过流式细胞术鉴定iNKT细胞。此外，在18例RR患者（11例接受NAT治疗，7例接受IFN治疗）、4例PP患者、6例SP患者和16例CTR患者中，评估了iNKT细胞在刺激后产生不同细胞因子（IL-17、TNF-α、IFN-γ和IL-4）的能力。
在不同MS类型的MS患者或不同治疗期间，iNKT细胞表型未发现主要差异。然而，iNKT细胞的多功能反应表现为Th1和Th17谱型。这在SP型患者中很明显，其特点是炎症和神经退行性变水平较高，且Th17细胞因子的产生持续增加以。接受NAT治疗的患者产生IL-17、TNF-α和IFN-γ的iNKT细胞水平较低。
我们的数据表明，疾病的进展期以iNKT细胞持续激活和向炎症表型倾斜为特征。与其他治疗相比，NAT能够调节iNKT细胞功能。
