Newly Found Rat CD103- Dendritic Cells Represent a Highly Immunogenic Subpopulation of Type-2 Conventional Dendritic Cells, Corresponding to Known Dendritic Cell Subsets in Mice and Humans.

Abstract

Dendritic cells (DCs), the primary antigen-presenting cells, have traditionally been identified by CD103 molecules in rats, whereas mouse and human DCs are identified by CD11c molecules. However, this history does not preclude the existence of CD103^- DCs in rats. To explore this possibility, we examined MHCII⁺ cells in rat spleen and thymus, identifying a novel population of CD103^-MHCII⁺CD45R^-CD172a⁺ cells. These cells are negative for CD103 and B cell marker CD45R, but positive for the type-2 conventional DC (cDC2) marker CD172a. Transcriptomic analyses revealed that they represent a subpopulation of cDC2. Additionally, gene set enrichment analysis predicted enhanced immunogenic activities for this novel population compared to known rat cDC2s. Mixed leukocyte reaction assays confirmed that the rat CD103^- cDC2s induce T cell proliferation more effectively than other DC subsets, suggesting enhanced immunogenic potential. In reaggregated thymic organ culture assays, both the rat CD103^- and CD103⁺ cDC2 subsets suppressed the total number of generated thymocytes and skewed the differentiation toward CD8 single-positive cells. Comparisons with previously published single-cell RNA-sequencing datasets showed that the rat CD103^- cDC2 subset shares markers and GO terms of known mouse and human cDC2 subpopulations: cDC2a, cDC2b, inf-cDC2, and moDC. In contrast, the classic rat CD103⁺ cDC2 subset expresses only cDC2a markers. These findings provide new insights into DC subpopulations, particularly in species other than mice and humans, where much remains to be uncovered.