Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103 and CD11b, which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages. cDC depletion abrogated antigen-specific CD8 T cell proliferative expansion, transforming subclinical cardiac injury to overt heart failure. These effects were mediated by CD103 cDCs, which are dependent on the transcription factor BATF3 for their development. Collectively, our findings identified resident cardiac cDC subsets, defined their origins, and revealed an essential role for CD103 cDCs in antigen-specific T cell responses during subclinical viral myocarditis.

In this study we evaluate macroporous scaffolds made of alginate-chitosan polyelectrolyte complexes (PEC) as tools to optimire the results of soft tissues oell therapy. Cell therapy using mesenchymal stem cells (MSC) bas become attractive for tissue repair and regeneration in a number of acute and chronic injuries. Unfortunately their low retention and/or survival after injection limit their beneficial effects. A biomaterial-assisted im plantation, providi ng oells a thr�mensional (3D) microenvironment is a promising strategy. To this purpose, we designed a family of PEC scaffolds, and studied if they could meet the requirement of such application. Xray tomography showed that ail PEC scaffolds present an interconnected macroporosity, and both rheology and tensile measurements reveal optimized mechanical properties (higher storage moduli and Young moduli) compared to alginate referenoe scaffolds. In vitro assays demonstrated their ability to allow MSC retention (higher than 90%) , lo ng-term viability and RiF2 secretion. Then, we used a skeletal muscle implantation mode! to assess the biological response to scaffolds graft, and showed that they support in vivo vascular formation within the implant-derived tissue. The combination of alginate/chitosan PEC scaffolds architecture and angio genic potential make them appear as interesti ng tools to optimize MSC therapy results in soft tissues.

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