In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived 
fibroblast-like cells called fibrocytes help to form scar tissue. Although 
fibrocytes promote collagen production by fibroblasts, little is known about 
signaling from fibroblasts to fibrocytes. In this report, we show that 
fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor 
necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that 
lumican, but not the related proteoglycan decorin, promotes human fibrocyte 
differentiation. Lumican competes with the serum fibrocyte differentiation 
inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte 
inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors 
that affect fibrocyte differentiation, lumican has no detectable effect on 
macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are 
needed for lumican-induced fibrocyte differentiation. In lung tissue from 
pulmonary fibrosis patients with relatively normal lung function, lumican is 
present at low levels throughout the tissue, whereas patients with advanced 
disease have pronounced lumican expression in the fibrotic lesions. These data 
may explain why fibrocytes are increased in fibrotic tissues, suggest that the 
levels of lumican in tissues may have a significant effect on the decision of 
monocytes to differentiate into fibrocytes, and indicate that modulating lumican 
signaling may be useful as a therapeutic for fibrosis.