Wright Pamela B, McEntegart Anne, McCarey David, McInnes Iain B, Siebert Stefan, Milling Simon W F
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow and.
Department of Rheumatology, Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow, UK.
Rheumatology (Oxford). 2016 Jan;55(1):120-32. doi: 10.1093/rheumatology/kev245. Epub 2015 Aug 28.
AS is a systemic inflammatory disease of the SpA family. Polymorphisms at loci including HLA-B27, IL-23R and ERAP-1 directly implicate immune mechanisms in AS pathogenesis. Previously, in an SpA model, we identified HLA-B27-mediated effects on dendritic cells that promoted disease-associated Th17 cells. Here we extend these studies to AS patients using deep immunophenotyping of candidate pathogenic cell populations. The aim of our study was to functionally characterize the immune populations mediating AS pathology.
Using 11-parameter flow cytometry, we characterized the phenotype and functions of lymphocyte and myeloid cells from peripheral blood, and the synovial phenotype of AS patients and age-matched healthy controls.
Significantly fewer circulating CD1c-expressing dendritic cells were observed in AS patients, offset by an increase in CD14(-) CD16(+) mononuclear cells. Ex vivo functional analysis revealed that this latter population induced CCR6 expression and promoted secretion of IL-1β and IL-6 when co-cultured with naive CD4(+) T cells. Additionally, systemic inflammation in AS patients significantly correlated with increased proportions of activated CCR9(+) CD4(+) T cells.
CD14(-) CD16(+) mononuclear cells may contribute to AS by promoting Th17 responses, and antigen-presenting cells of mucosal origin are likely to contribute to systemic inflammation in AS.
强直性脊柱炎（AS）是脊柱关节炎（SpA）家族中的一种全身性炎症性疾病。包括HLA - B27、IL - 23R和ERAP - 1等位点的多态性直接涉及AS发病机制中的免疫机制。此前，在一个SpA模型中，我们发现HLA - B27对树突状细胞有介导作用，可促进与疾病相关的Th17细胞。在此，我们通过对候选致病细胞群体进行深度免疫表型分析，将这些研究扩展至AS患者。我们研究的目的是从功能上表征介导AS病理的免疫群体。
我们使用11参数流式细胞术，对AS患者和年龄匹配的健康对照者外周血中的淋巴细胞和髓样细胞的表型及功能，以及滑膜表型进行了表征。
在AS患者中观察到循环中表达CD1c的树突状细胞显著减少，而CD14(-)CD16(+)单核细胞增加，抵消了这种减少。体外功能分析显示，当与初始CD4(+)T细胞共培养时，后一种细胞群体可诱导CCR6表达并促进IL - 1β和IL - 6的分泌。此外，AS患者的全身炎症与活化的CCR9(+)CD4(+)T细胞比例增加显著相关。
CD14(-)CD16(+)单核细胞可能通过促进Th17反应而导致AS，并且黏膜来源的抗原呈递细胞可能在AS的全身炎症中起作用。
