Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Ann Rheum Dis. 2013 Oct;72(10):1700-7. doi: 10.1136/annrheumdis-2012-202373. Epub 2013 Jan 17.
Interleukin (IL)-17A and Th17 cells are critically involved in T cell-mediated synovial inflammation. Besides IL-17A, Th17 cells produce IL-22. Recently, Th22 cells were discovered, which produce IL-22 in the absence of IL-17. However, it remains unclear whether IL-22 and Th22 cells contribute to T cell-mediated synovial inflammation. Therefore, we examined the potential of IL-22 and Th22 cells to induce synovial inflammation and whether IL-22 is required for T cell-mediated experimental arthritis.
Peripheral and synovial Th17 and Th22 cells were identified and sorted from patients with rheumatoid arthritis (RA). Co-culture experiments of these primary T cell populations with RA synovial fibroblasts (RASF) were performed. The in vivo IL-22 contribution to synovial inflammation was investigated by inducing T cell-mediated arthritis in IL-22 deficient mice and wild-type mice.
Peripheral Th17 and Th22 cell populations were increased in patients with RA and present in RA synovial fluid. In T cell-RASF co-cultures, IL-22 in the presence of IL-17A had limited effects on IL-6, IL-8, matrix metalloproteinase-1 (MMP-1) and MMP-3 production. Furthermore, primary peripheral blood and synovial Th17 cells were more potent in the induction of these factors by RASF compared with Th22 cells. In line with this, similar synovial inflammation and disease severity was found between IL-22 deficient and wild-type mice in T cell-mediated experimental arthritis.
These findings show that IL-17A/Th17 cell-mediated synovial inflammation is independent of IL-22 and Th22 cells. This implies that targeting IL-17A/Th17 cells, rather than IL-22/Th22 cells, should be the focus for treatment of T cell-mediated synovial inflammation.
白细胞介素（IL）-17A 和 Th17 细胞在 T 细胞介导的滑膜炎症中起着至关重要的作用。除了 IL-17A 之外，Th17 细胞还会产生 IL-22。最近，发现了 Th22 细胞，它们在没有 IL-17 的情况下产生 IL-22。然而，IL-22 和 Th22 细胞是否有助于 T 细胞介导的滑膜炎症尚不清楚。因此，我们研究了 IL-22 和 Th22 细胞诱导滑膜炎症的潜力，以及 IL-22 是否是 T 细胞介导的实验性关节炎所必需的。
从类风湿关节炎（RA）患者中鉴定和分选外周和滑膜 Th17 和 Th22 细胞。将这些原代 T 细胞群与 RA 滑膜成纤维细胞（RASF）进行共培养实验。通过在 IL-22 缺陷型和野生型小鼠中诱导 T 细胞介导的关节炎，研究体内 IL-22 对滑膜炎症的贡献。
RA 患者外周血 Th17 和 Th22 细胞群增加，存在于 RA 滑膜液中。在 T 细胞-RASF 共培养中，IL-17A 存在时 IL-22 对 IL-6、IL-8、基质金属蛋白酶-1（MMP-1）和 MMP-3 的产生仅有有限的影响。此外，与 Th22 细胞相比，原代外周血和滑膜 Th17 细胞更能诱导 RASF 产生这些因子。与此一致，在 T 细胞介导的实验性关节炎中，IL-22 缺陷型和野生型小鼠之间的滑膜炎症和疾病严重程度相似。
这些发现表明，IL-17A/Th17 细胞介导的滑膜炎症不依赖于 IL-22 和 Th22 细胞。这意味着针对 IL-17A/Th17 细胞，而不是 IL-22/Th22 细胞，应该是治疗 T 细胞介导的滑膜炎症的重点。
