Wound healing is impaired in older individuals, partly due to a persistent increase in immune cells called neutrophils. This study has found that the signalling molecule CCL3 is responsible for this persistent increase, and targeting it offers therapeutic potential to improve healing. Skin wound healing is a highly coordinated process involving a series of overlapping phases. In healthy tissue, inflammation is carefully controlled and eventually gives way to tissue repair. With age, however, this transition can become disrupted, leading to prolonged inflammation, delayed healing and, in some cases, chronic non-healing wounds.Inflammation is an essential early stage of wound repair. It helps protect against infection and clear damaged tissue, with neutrophils among the first immune cells recruited to the wound. These cells respond to signalling molecules, including CCL3, and play an important role in host defence.However, when healing is impaired, neutrophils can remain in the wound for too long, contributing to persistent inflammation. Until now, it has been unclear what drives this continued accumulation.CCL3 drives persistent neutrophil recruitmentIRR researchers led by the Cash lab found sustained CCL3 signalling molecules in wounds from aged mice and humans. CCL3 helps direct immune cells to specific locations in the body.They also found that young wounds transitioned from inflammatory to reparative programs as healing progressed. In contrast, aged wounds retained inflammatory signatures, with CCL3 levels remaining elevated.The researchers also found that neutrophils in aged wounds were not only more numerous, but were preferentially located around blood vessels. This suggests that neutrophils continue to be recruited from the circulation, rather than simply failing to be cleared from the wound.This distinction is important because it points towards a targeted therapeutic approach. Instead of broadly suppressing the immune response, it may be possible to modulate the inflammatory signals responsible for continued neutrophil recruitment while preserving the essential early immune response.Blocking CCL3 improves wound healingThe researchers tested this approach by blocking CCL3 signalling after the initial inflammatory response. This reduced the accumulation of neutrophils later in the healing process, accelerated wound closure and restored key features of healing that are impaired with age. We’ve found that persistent CCL3 expression is a contributor to sustained neutrophil recruitment and impaired repair in advanced age. Therapeutically targeting this pathway offers a way to restore timely resolution and improve healing outcomes. Dr Jenna Cash IRR Group Leader and the paper’s corresponding author Microscopy image showing cells within a wound site. There is a reduction in wound neutrophil (yellow) infiltration in wounds treated with CCL3 blocker (right) compared to those without CCL3 blocker (left). Next stepsThe researchers will now investigate how CCL3 drives persistent neutrophil accumulation. Future work will determine whether CCL3 directly interferes with neutrophil clearance, promotes repeated recruitment from the circulation, or does both.The team will also investigate how CCL3 acts on neutrophils. They identified the receptor CCR1 on wound neutrophils, raising the possibility that CCL3 binds to CCR1 to promote continued neutrophil recruitment. Understanding this mechanism could help identify more precise ways to target the pathway and improve wound healing in older tissue.Related linksRead the full paper in Frontiers in ImmunologyCash research group Tags CIR This article was published on Wednesday 23 September 2026
