Interleukin-22 Secreted by NKp44+ Natural Killer Cells Promotes Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.
Interleukin-22 Secreted by NKp44+ Natural Killer Cells Promotes Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.
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DOI：
10.1097/md.0000000000002137
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发表时间：
2015-12
期刊：
影响因子：
1.6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Zhu J;Jia E;Zhou Y;Xu J;Feng Z;Wang H;Chen X;Li J
尽管CD 3-CD 56 + NKp 44 +NK细胞与自身免疫性疾病（包括炎症性肠病、强直性脊柱炎和原发性干燥综合征）有关，但这些细胞在类风湿性关节炎（RA）患者中的扩增和作用仍不太明确。在这里，我们调查的比例NKp 44 +NK细胞在RA患者的发病机制。结果表明，RA患者外周血和关节液中NKp 44 +NK细胞明显扩增，且与RA病情活动度呈正相关。它们在RA滑膜组织中也高度表达，并在体外分泌高浓度的白细胞介素-22（IL-22）。此外，NKp 44 +NK细胞培养上清液促进成纤维细胞样滑膜细胞（FLS）的增殖，这被IL-22拮抗剂和AG 490阻断。经重组人IL-22处理后，RA-FLS细胞增殖和磷酸化STAT 3呈剂量依赖性和时间依赖性增加，AG 490可阻断其进程。本研究首次阐明了NKp 44 +NK细胞在RA患者外周血和滑液中的扩增，特别是在RA的滑膜组织中。STAT 3是介导NKp 44 +NK细胞分泌的IL-22对RA患者FLS增殖影响的重要途径。
Although CD3-CD56+NKp44+ natural killer (NKp44+NK) cells have been linked to autoimmune diseases including inflammatory bowel disease, ankylosing spondylitis, and primary Sjogren syndrome, the expansion and role of those cells in patients with rheumatoid arthritis (RA) remain less defined. Here, we investigate the proportion and pathogenesis of NKp44+NK cells in patients with RA. The results show NKp44+NK cells significantly expanded in RA peripheral blood and synovial fluid, which were correlated positively with RA disease activity. They also highly expressed in RA synovial tissues and secreted a high concentration of interleukin-22 (IL-22) in vitro. Further, NKp44+NK cells culture supernatant promoted the proliferation of fibroblast-like synoviocytes (FLS) which was blocked by IL-22 antagonist and AG490. Treated with recombination human IL-22, the proliferation and phosphorylation-STAT3 on RA-FLS increased in a dose-dependent manner and time-dependent manner; the progress of which could be blocked by AG490. The present study clarifies the expansion of NKp44+NK cells in the peripheral blood and synovial fluid of patients with RA, especially in the synovial tissues of RA for the first time. STAT3 is an essential pathway in mediating the effects of IL-22 secreted by NKp44+NK cells on the proliferation of FLS in patients with RA.