Ehrenstein, MR; Notley, CA; Brown, MA; McGovern, JL; Jordan, CK; (2015) Engulfment of activated apoptotic cells abolishes TGFβ mediated immunoregulation via the induction of IL-6. Journal of Immunology , 194 (4) pp. 1621-1627. 10.4049/​jimmunol.1401256.

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Abstract

Phagocytosis of apoptotic cells (AC) is usually a potent immunoregulatory signal but can also promote inflammation. Here, we show that administration of apoptotic dendritic cells (DC) inhibited inflammation in vivo through increasing production of TGFβ from intrinsic DC and B cells. However, AC derived from LPS activated DC (aAC) failed to restrain inflammation due to a short-lived but marked IL-6 response, which abolished the rise in TGFβ. Inhibition of IL-6 restored the protective anti-inflammatory properties of aAC and the TGFβ response. DC isolated from mice which had received resting but not activated AC could transfer the suppression of inflammation to recipient mice. These transferred DC stimulated B cell TGFβ production and relied upon 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 TGFβ.

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