Immunomodulation by adoptive regulatory T‐cell transfer improves Coxsackievirus B3‐induced myocarditis

What is it about?

Myocarditis is a cardiac inflammatory disorder, which is mainly caused by a viral infection of the heart. So far, specific treatment options are lacking, indicating the need for the development of new therapeutic strategies. Regulatory T cells (Tregs) offer new therapeutic options to control undesired systemic and local immune responses. The aim of this study was to determine the impact of a therapeutic Tregs administration on systemic and cardiac inflammation and function in an experimental model of virus-induced myocarditis, i.e. in Coxsackievirus B3 (CVB3)-induced myocarditis mice. Therefore, murine Tregs were isolated and applied in the vein of male CVB3-infected mice 3 days after infection. Compared to mice receiving only the buffer in which the cells are suspended (CVB3+PBS), mice receiving Tregs (CVB3+Tregs) exhibited a reduced cardiac presence of pro-inflammatory monocytes and a higher retention of pro-inflammatory monocytes in the spleen. Additionally, the production of monocytes in the spleen, the reservoir from which the monocytes migrate towards the heart, was reduced in CVB3+Tregs versus CVB3+PBS mice. Co-culture of splenocytes with Tregs further demonstrated the ability of Tregs to modulate monocyte differentiation in favour of the anti-inflammatory monocyte subset. The Tregs-mediated immunomodulation was paralleled by lower deposition of rigid collagen in the heart of CVB3+Tregs versus CVB3+PBS mice. In agreement with these findings, cardiac function was improved in CVB3+Tregs compared to CVB3+PBS mice. In conclusion, adoptive Tregs transfer in the inflammatory phase of viral-induced myocarditis protects the heart against inflammatory damage and the formation of fibrous tissue via modulation of monocyte subsets.

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