Stabilin‐1 (Stab1) and Stabilin‐2 (Stab2) are scavenger receptors expressed by liver sinusoidal endothelial cells (LSECs). The Stabilin‐mediated scavenging function is responsible for regulating the molecular composition of circulating blood in mammals. Stab1 and Stab2 have been shown to influence fibrosis in liver and kidneys and to modulate inflammation in atherosclerosis. In this context, circulating and localized TGFBi and POSTN are differentially controlled by the Stabilins as their receptors. To assess Stab1 and Stab2 functions in inflammatory and fibrotic skin disease, topical Imiquimod (IMQ) was used to induce psoriasis‐like skin lesions in mice and Bleomycin (BLM) was applied subcutaneously to induce scleroderma‐like effects in the skin. The topical treatment with IMQ, as expected, led to psoriasis‐like changes in the skin of mice, including increased epidermal thickness and significant weight loss. Clinical severity was reduced in Stab2‐deficient compared to Stab1‐deficient mice. We did not observe differential effects in the skin of Stabilin‐deficient mice after bleomycin injection. Interestingly, treatment with IMQ led to a significant increase of Stabilin ligand TGFBi plasma levels in Stab2−/− mice, treatment with BLM resulted in a significant decrease in TGFBi levels in Stab1−/− mice. Overall, Stab1 and Stab2 deficiency resulted in minor alterations of the disease phenotypes accompanied by alterations of circulating ligands in the blood in response to the disease models. Stabilin‐mediated clearance of TGFBi was altered in these disease processes. Taken together our results suggest that Stabilin deficiency‐associated plasma alterations may interfere with preclinical disease severity and treatment responses in patients.
Stabilin‐1 and Stabilin‐2 deficiency in mouse models of skin disease revealed altered circulating ligands but only minor alterations in disease phenotypes. Psoriasis‐like changes are reduced in Stab2‐deficient mice with increased TGFBi levels compared to Stab1‐deficient mice, while scleroderma‐like effects show no differential impact. These findings highlight Stabilins' role in modulating disease severity and circulating ligand dynamics, potentially impacting treatment strategies.