CD26 Identifies a Subpopulation of Fibroblasts that Produce the Majority of Collagen during Wound Healing in Human Skin

Fibroblasts produce collagens and other proteins that form the bulk of the extracellular matrix (ECM) in connective tissues. Emerging data point to functional heterogeneity of fibroblasts. However, the lack of subtype-specific markers hinders our understanding of the different roles of fibroblasts in ECM biology, wound healing, diseases, and aging. We have investigated the utility of the cell surface protein CD26 to identify functionally distinct fibroblast subpopulations in human skin. Using flow cytometry and immunohistology, we found that CD26, in combination with the cell surface glycoprotein CD90, identifies a distinct subpopulation of cells, which express relatively high levels of COL1A1, a hallmark of fibroblasts. Importantly, the population of CD26+ fibroblasts is selectively increased after wounding of human skin. These cells account for the majority of COL1A1 expression during the ECM remodeling phase of healing. The proportion of CD26+ fibroblasts in the skin of young and aged individuals is similar, indicating that the loss of collagen production during aging does not involve selective reduction of CD26+ fibroblasts. In culture, the majority of freshly isolated CD26− fibroblasts gain expression of CD26+. Taken together, these data provide a foundation for targeting CD26+ fibroblasts to modulate wound healing in human skin. Fibroblasts produce collagens and other proteins that form the bulk of the extracellular matrix (ECM) in connective tissues. Emerging data point to functional heterogeneity of fibroblasts. However, the lack of subtype-specific markers hinders our understanding of the different roles of fibroblasts in ECM biology, wound healing, diseases, and aging. We have investigated the utility of the cell surface protein CD26 to identify functionally distinct fibroblast subpopulations in human skin. Using flow cytometry and immunohistology, we found that CD26, in combination with the cell surface glycoprotein CD90, identifies a distinct subpopulation of cells, which express relatively high levels of COL1A1, a hallmark of fibroblasts. Importantly, the population of CD26+ fibroblasts is selectively increased after wounding of human skin. These cells account for the majority of COL1A1 expression during the ECM remodeling phase of healing. The proportion of CD26+ fibroblasts in the skin of young and aged individuals is similar, indicating that the loss of collagen production during aging does not involve selective reduction of CD26+ fibroblasts. In culture, the majority of freshly isolated CD26− fibroblasts gain expression of CD26+. Taken together, these data provide a foundation for targeting CD26+ fibroblasts to modulate wound healing in human skin.