Mesenchymal Cells of the Intestinal Lamina Propria

Abstract

The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow–derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ascribed solely to subepithelial myofibroblasts. We review the functional anatomy of intestinal mesenchymal cells and describe what is known about their origin in the embryo and their replacement in adults. As part of their putative role in intestinal mucosal morphogenesis, we consider the intestinal stem cell niche. Lastly, we review emerging information about myofibroblasts as nonprofessional immune cells that may be important as an alarm system for the gut and as a participant in peripheral immune tolerance.

Intestinal myofibroblast-specific Tpl2-Cox-2-PGE 2 pathway links innate sensing to epithelial homeostasis

“…7A), which is indicative of a potentially active involvement of these populations in disease processes. Subepithelial IMFs are a major α-SMA + mesenchymal cell type in the lamina propria showing high plasticity and a complex origin from several other mesenchymal but also nonmesenchymal cell types (23). The above analyses performed in mouse models strongly suggest a cell-specific homeostatic role of the Tpl2 pathway in IMFs.…”

“…In addition, NLRP6, which also plays a homeostatic role in the gut, is highly expressed in IMFs (46). This key role of IMFs in epithelial homeostasis can be explained by their subepithelial localization and their physiological implication in mechanisms of epithelial proliferation and differentiation during development (23,26). IMFs are in close proximity to the crypts participating in the construction of the stem cell niche (23,24) where they secrete growth factors and morphogens required in developmental processes (25).…”

“…To examine the cellular pathways mediating the homeostatic role of Tpl2 in the colon we generated mice bearing myeloid lineage-specific Tpl2 ablation (Tpl2 MYEL-KO ) using LysMCre (21) Intestinal subepithelial myofibroblasts (IMFs) are mesenchymal cells which underlie the epithelium in close proximity to the crypts, where they participate in stem cell niche formation and developmental processes (23)(24)(25)(26). To examine whether the reduction of Sox9 + cells and the defective epithelial proliferation in Tpl2 D/D mice result from a mesenchymal cell-mediated mechanism, we used ColVICre transgenic mice, which express Cre recombinase in IMFs (27), to generate ColVICreTpl2 FL/FL mice (Tpl2 IMF-KO ) bearing inactivation of Tpl2 in IMFs as shown previously (28).…”

“…To examine the distribution of intestinal myofibroblasts in the colon upon epithelial injury we treated WT mice with DSS and performed immunostainings against alpha smooth muscle actin (α-SMA), a microfilament protein expressed by myofibroblasts but also by pericytes, muscularis mucosae smooth muscle cells, and lymphatic lacteal-associated smooth muscle cells of the lamina propria (23). We observed that the network of α-SMA + mesencymal cells of the lamina propria is reorganized in the colon of DSS-treated mice in association with tissue damage progression.…”

Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1)

“…Remarkable progress has been made in identifying and characterizing intestinal stem cells but their particular niches remain poorly defined. The intestinal crypt is surrounded by subepithelial myofibroblasts, which are believed to secrete paracrine signals that regulate neighboring stem cells (8). In addition, Wnt factors have been clearly shown to be absolutely required within the intestinal stem cell niche.…”