Contrôle de la résolution de l'inflammation par les basophiles dans un modèle de lésion cutanée chez la souris âgée
Pro-resolution M2-like macrophages are critical for wound healing. Aging-associated systemic chronic inflammation alters their functions and favors the development of chronic wounds, a major morbidity in elderly patients. Basophils, rare circulating granulocytes known for their pro-inflammatory roles in allergic and parasitic diseases, can potently promote M2-like macrophage’s pro-resolution functions due to their high innate production of type 2 cytokines.
In this work in progress, we explore the roles of basophils in skin wound healing using mice models of specific basophil depletion or gene deletion, and reanalysis of published transcriptomic datasets. We show that basophils infiltrate skin wounds early during inflammation and express Interleukin 4 (IL-4) for at least three weeks. They inhibit the accumulation of pro-inflammatory monocytes/macrophages during the resolution phase in an IL-4 dependent manner and accelerate wound closure while favoring keratinocyte differentiation during re-epithelialization.In aged mice, basophils have a more activated and immature phenotype but unexpectedly show enhanced pro-resolution properties.
Thus, basophils display pro-resolution properties favoring the skin wound healing response in both adult and elder mice. Unraveling the molecular mechanisms controlling these properties may hold promise to restore optimal healing and resolution in the elderly.
Pour en apprendre davantage
CR CNRS au Centre de Recherche sur l’Inflammation à Paris, dans l’équipe de Nicolas Charles et Ulrich Blank “Basophiles, mastocytes et Immunopathologie”