Immune niches orchestrated by intestinal mesenchymal stromal cells lining the crypt-villus

Abstract

The mammalian intestine is an organ that can be spatially defined by two axes: longitudinal and vertical. Such anatomical structure ensures the maintenance of a relatively immuno-quiescent and proliferation-promoting crypt for intestinal stem cell differentiation while actively warding off the invading intestinal microbes at the villus tip during digestion and nutrient absorption. Such behavior is achieved by the fine coordination among intestinal epithelial cells, intestinal mesenchymal stromal cells and tissue-resident immune cells like myeloid cells and lymphocytes. Among these cell types resided in the colon, intestinal mesenchymal stromal cells are considered to be the essential link between epithelium, vasculature, neuronal system, and hematopoietic compartment. Recent advancement of single cell and spatial transcriptomics has enabled us to characterize the spatial and functional heterogeneity of intestinal mesenchymal stromal cells. These studies reveal distinctive intestinal mesenchymal stromal cells localized in different regions of the intestine with diverse functions including but not limited to providing cytokines and growth factors essential for different immune cells and epithelial cells which predict niche formation for immune function from the villus tip to the crypt bottom. In this review, we aim to provide an overall view of the heterogeneity of intestinal mesenchymal stromal cells, the spatial distribution of these cells along with their interaction with immune cells and the potential regulatory cytokine profile of these cell types. Summarization of such information may enrich our current understanding of the immuno-regulatory functions of the newly identified mesenchymal stromal cell subsets beyond their epithelial regulatory function.

Subepithelial Stromal Cells: Their Roles and Interactions with Intestinal Epithelial Cells during Gut Mucosal Homeostasis and Regeneration

“…By E14.5, the pseudostratified epithelium undergoes extensive remodeling into a columnar epithelium, which leads to the emergence of a villus structure. To gain insights into the underlying factors that potentially shape fetal gut compartments at this stage, Maimets et al reported that CD29 and PDGFRα + cells are crucial for fetal gut vilification [ 20 , 46 , 68 , 111 , 114 ]. The CD29 + cells expressed high Acta2, Myl4, Des, and LRIG1 levels, which could be the progenitor for fetal gut muscularis mucosa cells.…”

Floxed Il1rl2 Locus with mCherry Reporter Element Reveals Distinct Expression Patterns of the IL-36 Receptor in Barrier Tissues

“…While these cells could be leukocytes [6], the presence of the IL-36R on fibroblasts has been implied by functional in vitro studies, e.g., [32,35]. Fibroblasts exhibit great heterogeneity in the intestines [36]; thus, to assess the cellular subtype of the mCherry-positive cells, we performed double stained immunofluorescence analyses for the leukocytes and the Il1rl2 reporter (Figure 5). All mCherry-positive cells were also stained for CD45, which identified them as leukocytes.…”

The reparative immunologic consequences of stem cell transplantation as a cellular therapy for refractory Crohn’s disease

“…Hub clusters interacted broadly with other intestinal cell clusters confirming the importance of myeloid, stromal and glial cells as regulators of intestinal homeostasis. [29][30][31][32] When comparing interactions in baseline samples to those obtained 6 months post-SCT the most notable increase occurred between hub clusters 17, 19, and 21 involving epithelial clusters 3 (epithelial stem cell), 4 (enterocyte) and 14 (enterocyte) (Figure 4A). Examination of ligand-receptor pairs revealed signals involving chemokines, extracellular matrix, growth factors and WNT pathway ligands.…”