Abstract 16353: Myosin-Primed Tolerogenic Dendritic Cells Ameliorate Experimental Autoimmune Myocarditis
Background: Autoimmunity plays an important role in the pathogenesis of viral myocarditis and giant cell myocarditis. Tolerogenic dendritic cells (tDCs) are used as anti-inflammatory and immunosuppressive targets in a number of autoimmune disease models, but their effect on experimental autoimmune myocarditis (EAM) has not been addressed. The aim of this study was to investigate whether tDC therapy in an EAM mouse model can suppress inflammatory myocarditis.
Methods: tDCs were generated by treating immature DCs (imDCs) with TNF-α and cardiac myosin. Mice with EAM were injected twice with tDCs (with a 1-week interval) at three doses (2х105, 1х106, or 2х106). The severity of myocarditis was histopathologically assessed. The phenotypes of the DC and regulatory T (Treg; FoxP3+CD4+CD25+) cell populations were determined by flow cytometry and the effect of tDCs on autoimmunity-inducing cytokines was examined by ELISA. To confirm the myosin-specific Treg cell expansion in vivo, antigen-unpulsed, antigen-mismatched (type II collagen-pulsed), or myosin-pulsed tDCs were vaccinated in the same way. On day 21, splenocytes from each mouse were cultured with myosin and the Tregl population was evaluated by flow cytometry.
Results: Myosin-pulsed tDCs displayed lower levels of DC-related surface markers and expressed higher levels of indoleamine 2,3-dioxygenase and IL-10 than mature DCs. Histopathological examination revealed that hearts from tDC (2х105, 1х106) treated mice showed markedly reduced myocardial inflammation compared with those of untreated EAM mice.
The Treg cell population, as measured by phenotype and FoxP3 mRNA levels, was markedly increased in the EAM mice that received myosin-pulsed tDC only.
Conclusion: Taken together, these results show for the first time that myosin-pulsed tDCs ameliorate EAM. These therapeutic effects by tDCs were mediated at least by enhanced myosin-specific Treg cell induction and anti-inflammatory cytokine secretion.
- © 2013 by American Heart Association, Inc.