Notley Clare A, Brown Mark A, McGovern Jenny L, Jordan Christine K, Ehrenstein Michael R
Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom.
Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom
J Immunol. 2015 Feb 15;194(4):1621-7. doi: 10.4049/jimmunol.1401256. Epub 2015 Jan 19.
Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. However, ACs derived from LPS-activated DCs failed to restrain inflammation because of a short-lived but marked IL-6 response, which abolished the increase in TGF-β. Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs and the TGF-β response. DCs isolated from mice that had received resting but not activated ACs could transfer the suppression of inflammation to recipient mice. These transferred DCs stimulated B cell TGF-β production and relied on an intact B cell compartment to limit inflammation. These results highlight how the activation state of AC governs their ability to control inflammation through reciprocal regulation of IL-6 and TGF-β.
凋亡细胞（ACs）的吞噬作用通常是一种强大的免疫调节信号，但也可促进炎症反应。在本文中，我们表明，给予凋亡树突状细胞（DCs）可通过增加内源性DCs和B细胞中TGF-β的产生来抑制体内炎症。然而，源自脂多糖激活的DCs的ACs由于短暂但显著的IL-6反应而未能抑制炎症，该反应消除了TGF-β的增加。抑制IL-6可恢复aACs的保护性抗炎特性和TGF-β反应。从接受静止而非活化ACs的小鼠中分离出的DCs可将炎症抑制作用传递给受体小鼠。这些转移的DCs刺激B细胞产生TGF-β，并依赖完整的B细胞区室来限制炎症。这些结果突出了AC的激活状态如何通过IL-6和TGF-β的相互调节来控制其控制炎症的能力。
