Analysis of the role of helminth TGF-β mimic in tissue repair

Abstract

Abstract Intestinal parasites express excretory/secretory (ES) molecules, which modulate the type-2 immune response, including anti-inflammatory and tissue repair mechanisms. TGF-β mimic (TGM), an ES molecule secreted by H. polygyrus (Hp), binds TGF-β receptors yet lacks structural homology to TGF-β and exhibits distinct receptor interactions. Studies suggest TGM generates higher expression of immunoregulatory Foxp3+ Tregs and decreased fibrotic markers in vitro compared to TGF-β. Host TGF-β also influences wound healing. In cutaneous wounds, effective tissue repair requires rapid suppression of inflammation and local production of wound healing factors. We investigated whether TGM modulates wound healing using an in vivo wound biopsy model during which TGM is injected beneath a Tegaderm® layer to mimic cutaneous wound treatment. We showed that TGM accelerates wound healing when applied to the wound surface at multiple doses and modulates the associated inflammatory response. LC-MS/MS analysis of TGM-treated wound exudate revealed increases in proteins mediating leukocyte chemotaxis and proliferation, collagen deposition and fibrotic regulation. There was also enhanced immune cell infiltration of alternatively activated CD206+F4/80+ macrophages and epithelial cells concurrent with accelerated wound closure. These macrophages are CD301b+ and are essential for effective wound healing and potentially regulating fibrosis. Our findings indicate that TGM can enhance skin wound healing through enhanced production of proteins facilitating wound repair and through recruitment of specific macrophage subsets. This study will investigate TGM as a potential novel and effective therapeutic option for enhanced wound healing.