Replacement of wounded skin requires the initially florid cellular response to abate and even regress as the dermal layer returns to a relatively paucicellular state. The signals that direct this "stop and return" process have yet to be deciphered. CXCR3 chemokine receptor and its ligand CXCL11/IP-9/I-TAC are expressed by basal keratinocytes and CXCL10/IP-10 by keratinocytes and endothelial cells during wound healing in mice and humans. In vitro, these ligands limit motility in dermal fibroblasts and endothelial cells. To examine whether this signaling pathway contributes to wound healing in vivo, full-thickness excisional wounds were created on CXCR3 wild-type (؉/؉) or knockout (؊/؊) mice. Even at 90 days, long after wound closure, wounds in the CXCR3 ؊/؊ mice remained hypercellular and presented immature matrix components. The CXCR3 ؊/؊ mice also presented poor remodeling and reorganization of collagen, which resulted in a weakened healed dermis. This in vivo model substantiates our in vitro findings that CXCR3 signaling is necessary for inhibition of fibroblast and endothelial cell migration and subsequent redifferentiation of the fibroblasts to a contractile state. These studies establish a pathophysiologic role for CXCR3 and its ligand during wound repair. Skin wound repair is a complex, highly orchestrated event consisting of an early hypercellular infiltrate that resolves over time, with loss of most of the regenerativephase dermal fibroblasts and vascular conduits.1 This reversion of the dermal cellularity is necessary for the maturation and strengthening of the matrix, which when lacking, leads to chronic wounds.2 This leaves open the question of which signals define both the transition from regeneration to resolution and the cellular involution that accompanies these changes.Wound repair requires the ordered immigration of fibroblasts into the provisional matrix and keratinocytes over this matrix. This immigration and replacement of the tissue appears to be under the influence of both soluble factors secreted first by platelets and then by inflammatory cell infiltrates, and also matrix components produced by these cells and the immigrated fibroblasts and endothelial cells. Among the latter, tenascin-C and thrombospondins seem to play a major role and thereby mark the immature, regenerative phase of wound healing. [3][4][5] These influence the functionality of the vasculogenesis by acting, directly or indirectly, through growth factor receptors.6,7 These events involve a degree of cellular dedifferentiation to enable migration and proliferation. During the remodeling phase, sufficient cells have migrated into the provisional dermal matrix to mature this structure and across the missing epidermal gap to re-establish a keratinocyte covering. These cells then differentiate into synthetic fibroblasts to produce a mature collagen I-rich dermis or basal keratinocytes primed to differentiate vertically. Interestingly, a fully repaired dermis is paucicellular compared with the regenerative phase, implying a sig...