Wound repair: role of immune–epithelial interactions

Abstract

The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair.

The contribution of interleukin-2 to effective wound healing

“…As stated before, sources of IL-2 in wounds include macrophages, lymphocytes, and keratinocytes. 8,10,11 These cells, as well as others found in wounds, are also capable of responding to IL-2. 8,25,51 Understanding how IL-2 interacts with cells within the wound environment will help clarify its potential roles within the wound site.…”

“…Additionally, macrophages have been shown to contribute to the recruitment of other cells, including immune and skin cell subtypes, to the wound site. 8,10,11 The role of lymphocytes in wound healing is less well-defined. However, it appears that B lymphocytes, T-helper cells (THC), and cytotoxic T lymphocytes (CTL) protect wounds from viruses.…”

“…7,10 The innate immune system, which reacts non-specifically to protect the body, is clearly implicated in the wound healing process. Innate immune factors involved in wound healing include neutrophils, macrophages, and a vast array of cytokines produced both at the wound site and throughout the body.…”

“…The process of wound healing can be considered to have multiple phases: the hemostatic phase, the inflammatory phase, the proliferative phase, and the remodeling phase ( Figure 1). [7][8][9][10] These phases overlap; there is no abrupt separation between the phases. However, these designations are useful for understanding the overall wound healing process.…”

A plant-made cholera toxin B subunit enhances mucosal wound healing and protects against ulcerative colitis and colon cancer.

“…For example, macrophages can remove bacteria that penetrate the epithelium and damaged tissue (190) and play an important role in enhancing late phase wound healing (191). Lamina propria-resident dendritic cells were previously shown to suppress the severity of DSS colitis (192).…”