Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy.
Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy.
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DOI：
10.1016/j.cyto.2014.10.031
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发表时间：
2015-07
期刊：
影响因子：
3.8
通讯作者：
Hamad, Abdel Rahim A.
中科院分区：
文献类型：
--
作者：
Saxena, Ankit;Khosraviani, Sam;Noel, Sanjeev;Mohan, Divya;Donner, Thomas;Hamad, Abdel Rahim A.
白细胞介素-10（IL-10）可以说是最有效的抗炎细胞因子。它由几乎所有的先天性和适应性免疫细胞产生。这些细胞也作为其靶点，表明IL-10的分泌和作用受到高度调节，可能是区室化的。与这一观点一致，针对全身施用IL-10以调节自身免疫性疾病（1型糖尿病、多发性硬化、类风湿性关节炎、牛皮癣）的各种努力产生了相互矛盾且很大程度上无关紧要的效果。另一方面，IL-10可促进体液免疫应答，增强B细胞上的II类表达并诱导免疫球蛋白（IG）产生。因此，认为系统性红斑狼疮（SLE）患者的高IL-10水平是致病的，其阻断可改善疾病。在这方面，我们回顾了临床前的发现和结果，最近的临床研究使用外源性IL-10治疗上述自身免疫性疾病。此外，鉴于IL-10补充的成功有限，我们建议未来的研究应扩展到调节递送模式之外，包括开发新的策略来保护和补充IL-10的内源性来源。作为一个例子，我们提供的证据表明，异常Fas介导的IL-10产生的B细胞的缺失颠覆了IL-10在自身免疫性糖尿病中的免疫调节作用，Fas途径的调节保护了IL-10产生的B细胞，并完全保护NOD小鼠免于发生疾病。
Interleukin-10 (IL-10) is arguably the most potent anti-inflammatory cytokine. It is produced by almost all the innate and adaptive immune cells. These cells also serve as its targets, indicating that IL-10 secretion and action is highly regulated and perhaps compartmentalized. Consistent with this notion, various efforts directed at systemic administration of IL-10 to modulate autoimmune diseases (type 1 diabetes, multiple sclerosis, rheumatoid arthritis, psoriasis) have produced conflicting and largely inconsequential effects. On the other hand, IL-10 can promote humoral immune responses, enhancing class II expression on B cells and inducing immunoglobulin (Ig) production. Consequently, the high IL-10 level in systemic lupus erythematosus (SLE) patients is considered pathogenic and its blockade ameliorates the disease. In this perspective, we review preclinical findings and results of recent clinical studies using exogenous IL-10 to treat the aforementioned autoimmune diseases. In addition, given the limited success of IL-10 supplementation, we suggest that future studies should be expanded beyond modulating the delivery modes to include developing new strategies to protect and replenish the endogenous sources of IL-10. As an example, we provide evidence that aberrant Fas-mediated deletion of IL-10-producing B cells subverts the immunoregulatory role of IL-10 in autoimmune diabetes and that modulation of the Fas pathway preserves the IL-10-producing B cells and completely protects NOD mice from developing the disease.
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影响因子：
16.2
作者：
American Diabetes Association
通讯作者：
American Diabetes Association
影响因子：
15.3
作者：
D'Andrea, A;Aste-Amezaga, M;Valiante, N M;Ma, X;Kubin, M;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
4.4
作者：
Denning, TL;Campbell, NA;Ernst, PB
通讯作者：
Ernst, PB
影响因子：
5.5
作者：
Correa, Ismael;Veny, Marisol;Salas, Azucena
通讯作者：
Salas, Azucena
影响因子：
3.2
作者：
Dagvadorj, Jargalsaikhan;Naiki, Yoshikazu;Yokochi, Takashi
通讯作者：
Yokochi, Takashi