Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6.
Bottom Line: 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.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.
Affiliation: Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom.Show MeSH
Related in: MedlinePlus
Mentions: It has previously been shown that transfer of thymically derived ACs at the time of immunization can suppress the development and severity of inflammatory arthritis through the production of IL-10 (10, 18). Given the differences we found with respect to cytokine production between ACs and aACs, we next sought to investigate whether both are equally potent at suppressing inflammation in vivo. We used the Ag-induced arthritis (AIA) model, which is IL-17 dependent (22, 23). Although ACs derived from resting DCs suppressed the development of AIA, activation of the DCs with LPS before apoptosis induction resulted in an inability to modulate arthritis development (Fig. 3A). ELISA (Fig. 3B) and flow cytometry (Fig. 3C–F) data show that suppression of arthritis was determined by the balance of IL-17 and TGF-β production, where decreased production of IL-17 by draining lymph node cells and an increase in TGF-β production by the splenocytes were protective. aAC transfer was neither able to suppress IL-17 responses in the lymph node nor boost TGF-β production by splenic B cells and DCs. IL-10 production by splenocytes was upregulated by aACs to a similar level observed by resting ACs (Fig. 3B, 3D).
Affiliation: Division of Medicine, Centre for Rheumatology, University College London, London WC1E 6JF, United Kingdom.