Alloantigen Infusion Activates the Transcriptome of Type 2 Conventional Dendritic Cells.

Recent studies have revealed novel molecular mechanisms by which innate monocytic cells acutely recognize and respond to alloantigen with significance to allograft rejection and tolerance. What remains unclear is the single-cell heterogeneity of the innate alloresponse, particularly the contribution of dendritic cell (DC) subsets. To investigate the response of these cells to exposure of alloantigen, C57BL/6J mice were administered live allogenic BALB/cJ splenic murine cells versus isogenic cells. In parallel, we infused apoptotic allogenic and isogenic cells, which have been reported to modulate immunity. Forty-eight hours after injection, recipient spleens were harvested, enriched for DCs, and subjected to single-cell mRNA sequencing. Injection of live cells induced a greater transcriptional change across DC subsets compared with apoptotic cells. In the setting of live cell infusion, type 2 conventional DCs (cDC2s) were most transcriptionally responsive with a Ccr2+ cDC2 subcluster uniquely responding to the presence of alloantigen compared with the isogenic control. In vitro experimentation confirmed unique activation of CCR2+ cDC2s following alloantigen exposure. Candidate receptors of allorecognition in other innate populations were interrogated and A type paired Ig-like receptors were found to be increased in the cDC2 population following alloexposure. These results illuminate previously unclear distinctions between therapeutic infusions of live versus apoptotic allogenic cells and suggest a role for cDC2s in innate allorecognition. More critically, these studies allow for future interrogation of the transcriptional response of immune cells in the setting of alloantigen exposure in vivo, encouraging assessment of novel pathways and previously unexamined receptors in this setting.

Emerging Roles for Dendritic Cells in Heart Failure.

The field of cardio-immunology has emerged from discoveries that define roles for innate and adaptive immune responses associated with myocardial inflammation and heart failure. Dendritic cells (DCs) comprise an important cellular compartment that contributes to systemic immune surveillance at the junction of innate and adaptive immunity. Once described as a singular immune subset, we now appreciate that DCs consist of a heterogeneous pool of subpopulations, each with distinct effector functions that can uniquely regulate the acute and chronic inflammatory response. Nevertheless, the cardiovascular-specific context involving DCs in negotiating the biological response to myocardial injury is not well understood. Herein, we review our current understanding of the role of DCs in cardiac inflammation and heart failure, including gaps in knowledge and clinical relevance.