Abstract Extravasation control of leukocytes and their functional fates are crucial to maintain tissue homeostasis. Leukocyte lineage origin regulates these processes that blood monocytes derived from PDGFRα+ embryonic progenitors (PDGFRα-lineage) extravasate more efficiently to inflamed skin than non-PDGFRα-lineage cells. Here we elucidated the underlying mechanism and their macrophage identity fates in skin. Spatial confocal imaging showed PDGFRα-lineage monocytes adhered better on venular endothelium than non-PDGFRα-lineage before trans-venular migration dependently on ICAM-1. At endothelial interface, more ICAM-1-aggregates were observed with PDGFRα-lineage monocytes and disruption with a Src-family kinases antagonist reduced adhesion advantage. Extravasated PDGFRα-lineage monocytes exhibited slower β1-integrin-dependent migration to interstitium and remained proximal to hypodermal capillaries. Skin-interstitial fibronectin binds integrin-α5 and activates Src-family kinases to suppress macrophage expression of S1-marking CD163. By accessing nearby vascular matrices, PDGFRα-lineage monocytes mitigated this effect and developed stronger S1-identity. Together, extravasation fate of PDGFRα-lineage monocyte/macrophage reveals the vasculatures foster S1-macrophage identity formation in skin.
Li et al. (Wed,) studied this question.