Srivastava Rupesh K, Tomar Geetanjali B, Barhanpurkar Amruta P, Gupta Navita, Pote Satish T, Mishra Gyan C, Wani Mohan R
National Centre for Cell Science, University of Pune Campus, Pune 411 007, India.
J Immunol. 2011 Feb 15;186(4):2262-72. doi: 10.4049/jimmunol.1002691. Epub 2011 Jan 17.
IL-3, a cytokine secreted by Th cells, functions as a link between the immune and the hematopoietic system. We previously demonstrated the potent inhibitory role of IL-3 on osteoclastogenesis, pathological bone resorption, and inflammatory arthritis. In this study, we investigated the novel role of IL-3 in development of regulatory T (Treg) cells. We found that IL-3 in a dose-dependent manner increases the percentage of Foxp3(+) Treg cells indirectly through secretion of IL-2 by non-Treg cells. These IL-3-expanded Treg cells are competent in suppressing effector T cell proliferation. Interestingly, IL-3 treatment significantly reduces the severity of arthritis and restores the loss of Foxp3(+) Treg cells in thymus, lymph nodes, and spleen in collagen-induced arthritis mice. Most significantly, we show that IL-3 decreases the production of proinflammatory cytokines IL-6, IL-17A, TNF-α, and IL-1 and increases the production of anti-inflammatory cytokines IFN-γ and IL-10 in collagen-induced arthritis mice. Thus, to our knowledge, we provide the first evidence that IL-3 play an important role in modulation of Treg cell development in both in vitro and in vivo conditions, and we suggest its therapeutic potential in the treatment of rheumatoid arthritis and other autoimmune diseases.
白细胞介素-3（IL-3）是一种由辅助性T细胞分泌的细胞因子，在免疫系统和造血系统之间起连接作用。我们之前已证明IL-3对破骨细胞生成、病理性骨吸收及炎性关节炎具有强大的抑制作用。在本研究中，我们探究了IL-3在调节性T（Treg）细胞发育中的新作用。我们发现，IL-3通过非Treg细胞分泌IL-2以剂量依赖的方式间接增加Foxp3(+) Treg细胞的百分比。这些经IL-3扩增的Treg细胞能够抑制效应T细胞增殖。有趣的是，在胶原诱导性关节炎小鼠中，IL-3治疗可显著减轻关节炎的严重程度，并恢复胸腺、淋巴结和脾脏中Foxp3(+) Treg细胞的缺失。最显著的是，我们发现IL-3可降低胶原诱导性关节炎小鼠中促炎细胞因子IL-6、IL-17A、TNF-α和IL-1的产生，并增加抗炎细胞因子IFN-γ和IL-10的产生。因此，据我们所知，我们首次提供证据表明IL-3在体外和体内条件下对Treg细胞发育的调节中均发挥重要作用，并且我们认为其在类风湿性关节炎和其他自身免疫性疾病的治疗中具有治疗潜力。
