IL‐17A promotes neutrophilic inflammation and disturbs acute wound healing in skin

Abstract

In the wound healing process, neutrophils are the first inflammatory cells to move to the wound tissues. They sterilize wounds by killing microbes, and they stimulate other immune cells to protect the host from infection. In contrast, neutrophil-derived proteases cause damage to host tissues, so neutrophils play dual opposite roles in wound healing. Interleukin-17A (IL-17A) is a proinflammatory cytokine that promotes the recruitment of these cells. The role of this cytokine in the wound healing process is not fully clarified. In the present study, therefore, we examined how defect in IL-17A production affected the wound healing in skin. IL-17A-knockout (KO) mice showed promoted wound closure, myofibroblast differentiation and collagen deposition and decreased the neutrophil accumulation compared with wild-type (WT) mice. In contrast, the administration of recombinant IL-17A led to delayed wound closure, low collagen deposition and accelerated neutrophilic accumulation. In addition, the treatment of IL-17A-administered mice with a neutrophil elastase inhibitor improved the wound repair to the same level as that of WT mice. These results indicated that IL-17A hampered the wound healing process and suggested that neutrophilic inflammation caused by IL-17A may be associated with impaired wound healing in skin.

Cox-2 inhibition potentiates mouse bone marrow stem cell engraftment and differentiation-mediated wound repair

“…A study by Tagaki et al revealed that IL-17A knockout mice had enhanced wound closure, collagen deposition and myofibroblast differentiation. In contrast, exogenous supplementation of IL-17 resulted in increased infiltration of neutrophils, lessened deposition of collagen and delayed wound closure [47]. Similarly, our study depicted an increased expression of Cox-2 and IL-17 upon BMSCTx in mice that was abrogated in the presence of celecoxib leading to enhanced engraftment of stem cells and wound closure.These results prompted us to elucidate the downstream mechanisms involved in Cox-2-mediated inflammation through IL-17.…”

Interleukin‐23 regulates interleukin‐17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization

“…Finally, IL‐17 and TNF‐α are reported to sustain neutrophil recruitment. The detrimental effects of neutrophils have also been previously reported (19), where neutrophil‐depleted mice had a significant improvement in acute wound closure. Both IL‐23 and IL‐17 deficiency resulted in reduced neutrophil numbers.…”

“…There is some discrepancy about the source of IL‐17 produced in the skin, with reports showing that macrophages, neutrophils, γδ Tcells, and T helper(T h )17 cells are able to express IL‐17 (12, 19, 20). Using a reporter mouse model, we labeled any cell that activated the promoter for IL‐17A with yellow fluorescent protein.…”

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

“…Interleukin-17A is a proinflammatory cytokine that promotes the recruitment of neutrophils during wound healing. In wound healing, it likely delays wound healing while enhancing an inflammatory response that would promote the removal of microbes [117]. TRAF3IP2 alters keratinocyte differentiation in the skin and inhibits response to IL-17 [118].…”