Site‐specific expression of CD11b and SIRPα (CD172a) on dendritic cells: implications for their migration patterns in the gut immune system

Abstract

Dendritic cells (DC) in the intestinal tract play a major role in directing the mucosal immune system towards tolerance or immunity. We analyzed whether different mucosal DC subsets in pigs have specific functions, localizations, or migration patterns in vivo. Therefore, we collected physiologically migrating DC by pseudo-afferent cannulation of the intestinal duct in eight Göttingen minipigs. Lymph DC were phenotypically and functionally characterized and compared to DC found on histological sections of porcine small intestine and mesenteric lymph nodes (MLN). Four different DC subpopulations were detected. Lamina propria (LP) DC were mainly CD11b + signal regulatory protein a (SIRPa) + , DC in Peyer's patches were mainly CD11b -/SIRPa + in subepithelial domes and CD11b -/SIRPa -in interfollicular regions, whereas MLN DC were largely CD11b + /SIRPa -. Of these four subsets, only the CD11b + /SIRPa + DC and the CD11b + / SIRPa -DC were present in lymph. This suggests that DC migration to MLN largely originates from the LP. Lymph DC expressed high levels of MHC class II and costimulatory molecules and had a low capacity for FITC-dextran uptake, indicating a mature phenotype. However, lymph DC did not induce PBMC proliferation in MLR, and migration was not significantly influenced by mucosal antigen application.

A distinct subset of intestinal dendritic cells responds selectively to oral TLR7/8 stimulation

“…However, by immuno-histochemistry and FACS analysis, there is no decrease in PP DC numbers ( [17] and unpublished observation). That DC do not migrate from the PP to the MLN under SS conditions has recently been suggested by studies in minipigs [11].…”

“…It is possible that CD172a high and CD172a int populations differ in their anatomical distribution in the gut, with CD172a high iL-DC being more accessible to R-848. Indeed, it has been shown in histochemical analysis of the GALT of minipigs that CD11b and CD172a can be used to distinguish DC from different areas of the gut [11]. In rats, CD172a high DC may be located in the proximal part of the ileum, a region where murine DC can extend processes into the lumen of the gut [27].…”

“…Using this system we have shown that intestinal lymph DC (iL-DC) collected directly from rat lymph in steady state (SS) are not a homogeneous population of cells but represent at least two phenotypically distinct subsets [10]. This is also true for afferent lymph DC in other species [11][12][13]. Importantly, we have also shown that this phenotypic heterogeneity correlates with different functions in vivo, as iL-DC expressing low levels of CD172a selectively carry apoptotic material derived from intestinal epithelial cells to the T cell areas of the mesenteric lymph nodes (MLN) [2].…”

NKT Cell-Dependent Amelioration of a Mouse Model of Multiple Sclerosis by Altering Gut Flora

“…43 The DCs in the LP would present orally applied antigens, migrate and enter the MLN. 44,45 Therefore, we wondered if the MLN might serve as the primary site where a contraction of Th17 cells takes place via mechanisms involving regulatory cells or changes of local cytokine milieu. However, the antibiotic treatment did not influence iNKT cells or Foxp3 ϩ regulatory T cells in the MLNs.…”

Natural alternatives to in-feed antibiotics in pig production: can immunomodulators play a role?

“…Indeed, a significant population of these cells contained particles of apoptotic cells (Huang et al, 2000). Phenotypic analyses of migrating DC in porcine pseudo-afferent intestinal lymph suggest that migration routes are mainly from the villous lamina propria to MLN, and from the sub-epithelial domes to the interfollicular regions of the PP (Bimczok et al, 2005).…”