Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities

Abstract

Swine skin is one of the best structural models for human skin, widely used to probe drug transcutaneous passage and to test new skin vaccination devices. However, little is known about its composition in immune cells, and among them dendritic cells (DC), that are essential in the initiation of the immune response. After a first seminal work describing four different DC subpopulations in pig skin, we hereafter deepen the characterization of these cells, showing the similarities between swine DC subsets and their human counterparts. Using comparative transcriptomic study, classical phenotyping as well as in vivo and in vitro functional studies, we show that swine CD163(pos) dermal DC (DDC) are transcriptomically similar to the human CD14(pos) DDC. CD163(pos) DDC are recruited in inflamed skin, they migrate in inflamed lymph but they are not attracted toward CCL21, and they modestly activate allogeneic CD8 T cells. We also show that CD163(low) DDC are transcriptomically similar to the human CD1a(pos) DDC. CD163(low) DDC migrate toward CCL21, they activate allogeneic CD8 and CD4 T cells and, like their potential human lung counterpart, they skew CD4 T cells toward a Th17 profile. We thus conclude that swine skin is a relevant model for human skin vaccination.

CD1− and CD1+ porcine blood dendritic cells are enriched for the orthologues of the two major mammalian conventional subsets

“…Transcriptomic and functional studies demonstrated that the CD163 low population expressed high levels of CD172a, were XCR1 negative, and shared gene expression with cDC2 suggesting they are the tissue resident equivalents of the CD1 + subpopulation described here. Likewise, the CD172a − cells were the only population to express XCR1, therefore likely to resemble the cDC1 population described in human and mouse and the CD1 − population described here3637.…”

“…With the intention of identifying cDC in the skin as targets for vaccination strategies others have demonstrated that porcine skin CD163 low cells share phenotypic and transcriptomic features consistent with the cDC2, and a CD172a − subset orthologous to cDC1 cells3536. Similar populations have also recently been identified in the porcine lung37.…”

Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics

“…Even under conditions where the experimental design is favorable to the use of hierarchical clustering, GSEA ensures of the robustness of interpretation. GSEA has been used by us and others to perform cross-species comparisons (5, 19, 29, 42, 76–78). GSEA notably displays advantages and drawbacks distinct from those of hierarchical clustering.…”

“…The cRNAs (600 ng) were fragmented and used for hybridization on custom-designed Agilent ovine and porcine arrays. Our arrays for sheep and pig were custom-designed based on the commercial ovine Agilent arrays for these two species, as previously described (28, 29). In brief, the commercial probes with poor Sigreannot scores (30) were replaced with new probes designed using the e-array software from Agilent Technologies and including ovine or porcine orthologs of genes known to be selectively expressed in human and mouse DC subsets (15).…”

Characterization and expression of DEC205 in the cDC1 and cDC2 subsets of porcine dendritic cells from spleen, tonsil, and submaxillary and mesenteric lymph nodes

“…Swine are an important animal model for human research due to their physiologic, anatomic and immunologic similarity. In the field of DCs, Marquet et al (2011Marquet et al ( , 2014 characterized the skin cDCs and found that the CD172a − XCR1 + (which is homologous to human BDCA3 + ) and CD172a + XCR1 − (homologous to human BDCA1 + ) subsets correspond to cDC1 and cDC2, respectively (Marquet et al, 2011;Marquet et al, 2014). Maisonnasse et al (2016a,b) described similar results in lung and bronchoalveolar lavage (Maisonnasse et al, 2016a;Maisonnasse et al, 2016b).…”