The Journal of Immunology Engulfment of Activated Apoptotic Cells Abolishes TGF-b–Mediated Immunoregulation via the Induction of IL-6

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-b 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-b. Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs and the TGF-b 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-b 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-b. The Journal of Immunology, 2015, 194: 1621–1627. T he rapid clearance of apoptotic cells (ACs) by phagocytes plays a central role in maintaining tissue homeostasis and immune tolerance to self-Ags (1–3). Defects or disruption to AC clearance can lead to the chronic accumulation of apoptotic material, the initiation of inflammation, and ultimately the devel-opment of autoimmunity or persistent inflammatory disease (4, 5)