Single-Cell Protein and RNA Expression Analysis of Mononuclear Phagocytes in Intestinal Mucosa and Mesenteric Lymph Nodes of Ulcerative Colitis and Crohn's Disease Patients.

Laurence Chapuy,Marika Sarfati

doi:10.3390/cells9040813

Abstract

Inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are driven by an abnormal immune response to commensal microbiota in genetically susceptible hosts. In addition to epithelial and stromal cells, innate and adaptive immune systems are both involved in IBD immunopathogenesis. Given the advances driven by single-cell technologies, we here reviewed the immune landscape and function of mononuclear phagocytes in inflamed non-lymphoid and lymphoid tissues of CD and UC patients. Immune cell profiling of IBD tissues using scRNA sequencing combined with multi-color cytometry analysis identifies unique clusters of monocyte-like cells, macrophages, and dendritic cells. These clusters reflect either distinct cell lineages (nature), or distinct or intermediate cell types with identical ontogeny, adapting their phenotype and function to the surrounding milieu (nurture and tissue imprinting). These advanced technologies will provide an unprecedented view of immune cell networks in health and disease, and thus may offer a personalized medicine approach to patients with IBD.

Highlights

Inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are driven by an abnormal immune response to commensal microbiota in genetically susceptible hosts
10% of conventional dendritic cells (cDCs)) [5,8]. cDC2 is classically divided into SIRPα+ CD103+ cDC2, which is the main subset in the small intestine in mice [9] and humans [5,10], and SIRPα+ CD103− cDC2, which predominates in the colon [5,8] (Figure 2)
DCs, which represent the main cDC population in Mesenteric lymph nodes (MLNs), are detected in larger proportion in CD than UC [66]. These data apparently contradict the results reported by Granot et al about a predominant cDC2 population in MLNs using CD11c+ as the parent gate [67]

Summary

Mononuclear Phagocytes in Intestinal Mucosa

Transcriptomic, and proteomic analyses have provided insights into redefining mononuclear phagocyte (MNP) classification and understanding the functional diversity of MNP subsets in tissue at homeostasis and during inflammation. MNPs are stratified into conventional dendritic cells (cDCs), embryonically-derived macrophages (Mφ), and monocyte-derived cells (MDC), an entity that regroups monocyte-derived DCs, monocyte-derived Mφ, and inflammatory monocyte-like cells [1,2,3,4] (Figure 1)

MNPs in Intestinal Mucosa at Steady State

MNPs in Intestinal Mucosa during Inflammation

Plasticity of Monocyte-Derived Cells in Human Inflamed Gut Mucosa

MNPs in MLNs of CD and UC patients

Findings

Conclusion and Future Perspectives