The role of angiopoietin-like 4 in IFN-g-mediated NETosis and inflammatory dynamics in the wound environment

Abstract

ANGPTL4, a matricellular protein, plays important roles in wound healing by regulating re-epithelialization and angiogenesis. Angptl4-/- mice exhibit impaired wound healing and an increased abundance of neutrophils linked to Ifng overexpression. However, the implications of these observations have remained enigmatic and are examined in detail in our study. To delineate the relationship between Angptl4 deficiency, Ifng expression, neutrophil, and wound healing, we compared IFN-γ protein levels between wound fluid of Angptl4+/+ and Angptl4-/- mice. We subsequently assessed IFN-γ’s impact on in vivo skin wounding, neutrophil abundance, and NETosis following IFN-γ blockade or adoptive transfer of IFN-γ-treated neutrophils. Our research findings highlight IFN-γ as a key mediator promoting heightened pro-inflammatory wound neutrophil levels and NETosis, which could hold great potential to be targeted to ameliorate chronic wounds in which ANGPTL4 expression is suppressed.