Inflammation, when it persists in an uncontrolled manner, exposes the body to pathological consequences such as fibrosis or the development of chronic wounds. The latter represent a frequent complication in elderly individuals, a population increasingly exposed to chronic inflammation. Yet skin wound healing is closely dependent on an active phase of inflammation resolution, defects in which specifically promote wound chronicity. In this context, the authors focused on the role of basophils, rare circulating granulocytes usually associated with allergic or autoimmune reactions and with their pro-inflammatory functions, but for which several studies had already suggested resolution-promoting properties in various tissues, including the skin.
Using immunofluorescence analyses and confocal imaging of murine skin wounds, the team shows that basophils accumulate in perivascular areas at the wound periphery for at least three weeks, spanning both the inflammatory phase and the resolution phase. To test their function, the researchers used a model of basophil depletion by diphtheria toxin. This depletion is accompanied by increased secretion of inflammatory molecules, by the accumulation and activation of pro-inflammatory leukocytes, and by delayed wound healing. Basophils in particular promote epidermal differentiation toward a homeostatic state, a property mediated notably by the interleukin-4 they produce. Reanalysis of a single-cell sequencing dataset, complemented by ligand–receptor interaction prediction, confirms the presence of basophils expressing pro-resolving mediators in wounds and the existence of IL-4 signaling networks directed toward several cell types.
Unexpectedly, the work reveals that, in aged mice (75 to 90 weeks), basophils infiltrate skin wounds more strongly and display a more activated phenotype than in adults. In this aging context as well, their depletion impairs inflammation resolution and wound closure, confirming their beneficial role. Basophils thus emerge as pro-resolution cells during skin wound healing, an essential biological process, in both adult and aged animals.
By establishing that basophils orchestrate inflammation resolution and promote wound healing, this work sheds light on a still poorly explored facet of these cells. According to the authors, a better understanding of their pro-resolution properties could open new avenues for combating chronic wounds in elderly individuals.