IL-3 Attenuates Collagen-Induced Arthritis by Modulating the Development of Foxp3+ Regulatory T Cells
IL-3 Attenuates Collagen-Induced Arthritis by Modulating the Development of Foxp3+ Regulatory T Cells
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DOI：
10.4049/jimmunol.1002691
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发表时间：
2011-02-15
影响因子：
4.4
通讯作者：
Wani, Mohan R.
中科院分区：
文献类型：
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作者：
Srivastava, Rupesh K.;Tomar, Geetanjali B.;Wani, Mohan R.
IL-3是Th细胞分泌的一种细胞因子，在免疫系统和造血系统之间起着连接作用。我们先前证实了IL-3对破骨细胞生成、病理性骨吸收和炎性关节炎的有效抑制作用。在这项研究中，我们研究了IL-3在调节性T（Treg）细胞发育中的新作用。我们发现IL-3以剂量依赖性方式通过非Treg细胞分泌IL-2间接增加Foxp 3（+）Treg细胞的百分比。这些IL-3扩增的Treg细胞能够抑制效应T细胞增殖。有趣的是，IL-3治疗显著降低了关节炎的严重程度，并恢复了胶原诱导的关节炎小鼠胸腺、淋巴结和脾脏中Foxp 3（+）Treg细胞的丢失。最重要的是，我们发现IL-3减少了胶原诱导的关节炎小鼠中促炎细胞因子IL-6、IL-17 A、TNF-α和IL-1的产生，并增加了抗炎细胞因子IFN-γ和IL-10的产生。因此，据我们所知，我们提供了第一个证据表明IL-3在体外和体内条件下调节Treg细胞发育中起重要作用，并且我们提出了其在治疗类风湿性关节炎和其他自身免疫性疾病中的治疗潜力。免疫学杂志，2011，186：2262-2272。
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-alpha, and IL-1 and increases the production of anti-inflammatory cytokines IFN-gamma 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. The Journal of Immunology, 2011, 186: 2262-2272.