The Beginning of the End: CXCR3 Signaling in Late-Stage Wound Healing.

BACKGROUND:Prior to 2009, research regarding the role of CXC receptor 3 (CXCR3) in cutaneous biology was primarily in the context of inflammatory reactions. Foundational research performed at that time demonstrated that, in addition to recruited inflammatory cells, cellular components of the skin, keratinocytes, fibroblasts, and endothelial cells, also express CXCR3 and are capable of expressing CXCR3 ligands, specifically CXC ligand 10 (CXCL10) and CXCL11. Surprisingly, in vitro experimentation demonstrated differential effects on the different cell types, suggesting that the CXCR3 signaling pathway may serve as a coordinator of wound remodeling. In support of this, a CXCR3 null mouse line and a mouse line abrogating CXCL11 expression in the epidermis demonstrated delayed wound closure and disordered dermal wound healing. THE PROBLEM:These findings demonstrate the role of CXCR3 signaling in the latter stages of wounding healing and opened a new avenue of investigation into the molecular and cellular mechanisms of coordinating the events of cutaneous tissue regeneration. BASIC SCIENCE ADVANCES:More recent investigation highlights the role of CXCR3 signaling in the dramatic vascular pruning events after the proliferative stage of wound healing and its importance in guiding remodeling of dermal collagen during cicatrix formation. CONCLUSION:CXCR3 signaling plays a strong role in coordinating the actions of several cell types during cutaneous wound healing. The disruption of this signaling pathway results in delayed return to homeostasis and dystrophic scarring.