Prostaglandin-secreting cells: a portable first aid kit for tissue repair

Abstract

After intestinal injury, both the number and type of intestinal epithelial cells must be restored. Intestinal stem cells, located at the base of the intestinal crypt, repopulate the depleted crypt in a process known as compensatory proliferation. In this issue of the JCI, Brown et al. describe a new mechanism by which this process is regulated (see the related article beginning on page 258). Surprisingly, they find that a subset of stromal cells present within the intestinal tissue and expressing the proliferative factor prostaglandin-endoperoxidase synthase 2 (Ptgs2) is repositioned next to the intestinal stem cell compartment where local production of PGE(2) controls injury-induced epithelial cell proliferation.

Figure 1. Model of MyD88-dependent relocalization of Ptgs2-expressing cells to the rectal crypt base and epithelial proliferation following DSS-induced injury.

(A) In the steady state, Ptgs2-expressing epithelial cells are mostly present in the lamina propria of the upper and middle regions of the rectal crypt. (B) Upon DSS-induced injury (i), these Ptgs2-expressing cells migrate to the bottom of the crypt, occupying a position near the stem cell niche (ii). This relocalization is dependent on MyD88 expression by leukocytes, presumably stimulated by TLR recognition of microbial products following barrier disruption. (C) Compensatory proliferation of stem cells and transit-amplifying (TA) epithelial cells after DSS-induced injury is dependent on MyD88 and Ptgs2, whereby a MyD88-dependent signal triggers repositioning of PGE₂-producing cells to the crypt base, adjacent to the stem cell compartment.