Transcriptional profiling reveals monocyte-related macrophages phenotypically resembling DC in human intestine

Abstract

The tissue dendritic cell (DC) compartment is heterogeneous, and the ontogeny and functional specialization of human tissue conventional DC (cDC) subsets and their relationship with monocytes is unresolved. Here we identify monocyte-related CSF1RFlt3 antigen presenting cells (APCs) that constitute about half of the cells classically defined as SIRPα DCs in the steady-state human small intestine. CSF1RFlt3 APCs express calprotectin and very low levels of CD14, are transcriptionally related to monocyte-derived cells, and accumulate during inflammation. CSF1RFlt3 APCs show typical macrophage characteristics functionally distinct from their Flt3 cDC counterparts: under steady-state conditions they excel at antigen uptake, have a lower migratory potential, and are inefficient activators of naïve T cells. These results have important implications for the understanding of the ontogenetic and functional heterogeneity within human tissue DCs and their relation to the monocyte lineage.

Resident memory CD8 T cells persist for years in human small intestine

“…It is likely that this treatment also affects the T cell numbers in the periphery. Second, solid organ transplantation surgery causes ischemia and reperfusion injury of the graft that increases the turnover of leukocytes (Eguiluz-Gracia et al, 2016); and third, our previous studies have shown that dendritic cells and some of the macrophage subsets are rapidly replaced in the transplanted duodenum Richter et al, 2018), thereby increasing the risk of local allo-reactivity. As shown by Zuber et al (Zuber et al, 2016) Most studies of SI CD8 T cells in humans have focused on the intraepithelial compartment, and there is less knowledge about the CD8 T cell population in LP.…”

“…Small intestinal samples were either obtained during pancreatic cancer surgery (Whipple procedure, n = 35; mean age 63yr; range 40-81yr; 16 female), or from donors and/or patients during pancreas-duodenum transplantation (donors: n = 52; mean age 31yr; range 5-55yr; 24 female; patients: n = 36; mean age 41yr; range 25-60yr; 14 female) as described previously (Landsverk et al, 2017;Richter et al, 2018). Endoscopic biopsies from donor and patient duodenum were obtained 3, 6 and 52 weeks after transplantation.…”

Resident memory CD8 T cells persist for years in human small intestine

“…Human biological material SI samples were obtained either during pancreatic cancer surgery (Whipple procedure, n = 35; mean age 63 yr, range 40-81; 16 female) or from donors or patients during pancreas-duodenum Tx (donors, n = 52; mean age 31 yr, range 5-55; 24 female; patients, n = 36; mean age 41 yr, range 25-60; 14 female) as described previously (Landsverk et al, 2017;Richter et al, 2018). Cancer patients receiving neoadjuvant chemotherapy were excluded from the study.…”

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

“…The first step to characterize intestinal Mfs by flow cytometry is gating on MNPs, i.e., CD45 + Lin −(CD3/CD19/CD56) HLA-DR int−hi CD14 neg−hi cells (Figures 3A, 4). Then, among MNPs, CD14 (Figures 3A, 4), CD64 and CD163 are used to distinguish Mfs from DCs (72,75,(221)(222)(223)(224)(225). To note, various studies have shown that CD64 alone was not sufficient to distinguish intestinal Mfs from DCs, as some cDC2 are CD64 + (72,135,220,224).…”