Hattori Koto, Tanaka Shigeru, Hashiba Daisuke, Tamura Jun, Etori Keishi, Kageyama Takahiro, Ito Takashi, Meguro Kazuyuki, Iwata Arifumi, Suto Akira, Suzuki Kotaro, Nakamura Junichi, Ohtori Seiji, Ziegler Steven F, Nakajima Hiroshi
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan.
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan; Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan.
J Autoimmun. 2024 Dec;149:103333. doi: 10.1016/j.jaut.2024.103333. Epub 2024 Nov 6.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic polyarthritis. It is well-established that helper T cells play crucial roles in the development and deterioration of RA. Recent studies also revealed the significant roles of regulatory T (Treg) cells in this context. Although Treg cells distributed in peripheral tissues exhibit various functions, the characteristics of synovial Treg cells remain unknown. In this study, we demonstrate that synovial Treg cells exacerbate synovial inflammation by reducing the number of immunoregulatory eosinophils through competitive consumption of IL-33. Synovial Treg cells expressed ST2 in a murine arthritis model, and surprisingly, Treg-specific ST2 knockout (ST2) mice exhibited attenuated arthritis. In ST2 mice, an increase in immunoregulatory synovial eosinophils was observed. Additionally, immunoregulatory eosinophils were found to express ST2, and ST2-expressing Treg cells controlled the abundance of immunoregulatory eosinophils, possibly by consuming IL-33. Our results highlight that a subset of synovial Treg cells possesses the machinery to worsen arthritis by suppressing eosinophils. In the future landscape where Treg cell-based therapies are employed for autoimmune diseases, it is important to comprehend the characteristics of disease-related Treg cells. Understanding these aspects is crucial for ensuring safer treatment modalities that do not inadvertently worsen the diseases.
类风湿性关节炎（RA）是一种以慢性多关节炎为特征的自身免疫性疾病。众所周知，辅助性T细胞在RA的发展和恶化中起着关键作用。最近的研究还揭示了调节性T（Treg）细胞在此过程中的重要作用。尽管分布在外周组织中的Treg细胞具有多种功能，但滑膜Treg细胞的特征仍不清楚。在本研究中，我们证明滑膜Treg细胞通过竞争性消耗IL-33减少免疫调节性嗜酸性粒细胞的数量，从而加剧滑膜炎症。在小鼠关节炎模型中，滑膜Treg细胞表达ST2，令人惊讶的是，Treg特异性ST2基因敲除（ST2KO）小鼠的关节炎症状有所减轻。在ST2KO小鼠中，观察到免疫调节性滑膜嗜酸性粒细胞增加。此外，发现免疫调节性嗜酸性粒细胞表达ST2，表达ST2的Treg细胞可能通过消耗IL-33来控制免疫调节性嗜酸性粒细胞的数量。我们的结果表明，滑膜Treg细胞的一个亚群具有通过抑制嗜酸性粒细胞而加重关节炎的机制。在未来将基于Treg细胞的疗法应用于自身免疫性疾病的前景中，了解疾病相关Treg细胞的特征非常重要。理解这些方面对于确保不会无意中加重疾病的更安全治疗方式至关重要。
