Regional Differences in Dendritic Cell Subsets, Phenotype and Function in the Healthy Human Colon

Information concerning dendritic cell (DC) distribution and function throughout the healthy human gastrointestinal (GI) tract is scarce. Eighty-four paired sets of proximal (right/ascending) and distal (left/descending) human colonic biopsies from healthy subjects were taken; DC subsets, phenotype and function were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. Colonic DC (CD45⁺DR⁺lineage^-) were myeloid (CD11c⁺CD123^-) and further distinguished according to CD103 and SIRPα expression: CD103^-SIRPα⁺ DC predominated and together with CD103⁺SIRPα⁺ DC were CD1c⁺ILT3⁺. By contrast, CD103⁺SIRPα^- DC constituted a minor subset of CD141⁺ILT3^- cells. Proximal colon had higher numbers of DC and fewer CD103⁺SIRPα⁺ cells. Proximal colonic DC were also more mature than distal DC with higher stimulatory capacity for CD4⁺CD45RA⁺ T-cells.  However, DC and DC-invoked T-cell expression of mucosal homing markers (β7, CCR9) was lower for proximal DC paralleled by lower e-Cadherin and CCL25 mRNA expression. Proximal colon produced higher levels of cytokines and carried a lower microbiota load but with no differences in microbiota composition between compartments. DC numbers were also higher in proximal than distal colon of C57BL/6 male mice but differences were abrogated in the absence of the microbiota in germ-free animals. Proximal colonic DC subsets differ from those in the distal colon being more mature. Studies addressing the immune system of the GI-tract should therefore reflect immune compartmentalization throughout the colon.