CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France.
CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, F-44000, France.
J Autoimmun. 2016 Jun;70:73-9. doi: 10.1016/j.jaut.2016.03.015. Epub 2016 Apr 18.
Mucosal associated invariant T cells (MAIT) and innate lymphoid cells (ILCs) have immunoregulatory functions at mucosal sites and have been involved in various inflammatory and autoimmune diseases. The aim of this study was to assess their frequencies in blood in ANCA-associated vasculitis (AAV).
The frequencies and function of MAIT cells, ILCs, γδT, iNKT, NK cells were analyzed by flow cytometry on PBMC of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) without any treatment, in acute (AP) and remission phase (RP) and compared with healthy controls (HC).
The frequencies of MAIT cells were strongly decreased in GPA and MPA in AP compared to HC, both in never treated and in relapsing patients and independently of patient age. This was associated with an activated phenotype of patient MAIT cells, as shown by increased expression of CD69 and IFNγ. MAIT cells remained decreased during RP in AAV patients. The frequencies of iNKT and γδT cells were unaffected compared to HC, whereas those of NK cells were slightly reduced during AP in MPA. We also observed a significant decrease in frequencies of total ILCs with decreased ILC2 and ILC3 and increased ILC1 during AP in both GPA and MPA compared to HC. These frequencies normalized during RP. Interestingly, we observed a significant correlation between the frequency of total ILCs and BVAS.
We show for the first time that AAV are associated with a major decrease and an activated phenotype of blood MAIT cell. These features persisted during remission suggesting a role for MAIT cells in the pathogenesis of AAV.
黏膜相关不变 T 细胞（MAIT）和固有淋巴细胞（ILC）在黏膜部位具有免疫调节功能，并参与各种炎症和自身免疫性疾病。本研究旨在评估其在抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）患者血液中的频率。
通过流式细胞术分析未经治疗、处于活动期（AP）和缓解期（RP）的肉芽肿性多血管炎（GPA）和显微镜下多血管炎（MPA）患者以及健康对照者（HC）外周血单个核细胞（PBMC）中 MAIT 细胞、ILC、γδT、iNKT、NK 细胞的频率和功能。
与 HC 相比，GPA 和 MPA 患者在 AP 时 MAIT 细胞频率明显降低，无论是初治患者还是复发患者，均与患者年龄无关。这与患者 MAIT 细胞的激活表型有关，表现为 CD69 和 IFNγ表达增加。AAV 患者在 RP 期间 MAIT 细胞仍减少。与 HC 相比，iNKT 和 γδT 细胞频率无变化，而 MPA 患者在 AP 时 NK 细胞略有减少。我们还观察到，与 HC 相比，在 GPA 和 MPA 患者的 AP 期间，总 ILC 频率显著降低，ILC2 和 ILC3 减少，ILC1 增加。这些频率在 RP 期间恢复正常。有趣的是，我们观察到总 ILC 频率与 BVAS 之间存在显著相关性。
我们首次表明，AAV 与血液 MAIT 细胞数量显著减少和激活表型有关。这些特征在缓解期仍存在，提示 MAIT 细胞在 AAV 发病机制中的作用。
