SCARF1 Deficiency Exacerbates Gut Inflammation and Autoimmune Pathology

Systemic lupus erythematosus (SLE) is a complex autoimmune disease known for its heterogeneity in both manifestation and presentation. Recent evidence has increasingly implicated the gut microbiome within immunomodulation and autoimmunity. This study aims to characterize the intestinal inflammation and microbial profile associated with autoimmune diseases, particularly SLE, and to identify unique biomarkers and shared microbial signatures for potential therapeutic measures. Our lab identified scavenger receptor class F, member 1 (SCARF1, SREC-1) as an efferocytosis receptor essential for the clearance of apoptotic debris, and its deficiency results in the development of lupus-like disease. SCARF1 is crucial in immune homeostasis, and defects in efferocytosis lead to inflammation. However, the role of SCARF1 in homeostasis in the gut remains to be elucidated. To answer our question, we analyzed and compared the metagenomic datasets generated through whole genome shotgun sequencing between our Scarf1 ^−/− lupus-prone mouse model and healthy counterparts. We found that Scarf1 ^−/− mice had significantly lengthened intestines, elevated immune cell infiltration, and structural changes in the colon. Microbiome analysis revealed gut dysbiosis, including reduced alpha diversity and increased F/B ratio. Notably, beneficial taxa such as Akkermansia muciniphila was absent in Scarf1 ^−/− mice. Linear regression analysis identified positive associations between lupus disease severity and increased abundances of Bacillota, Alistipes, Lachnospiraceae , and Hominisplanchenecus . Function analysis of the gut microbiome in Scarf1 ^−/− mice indicated downregulation of multiple pathways related to cell proliferation. These findings highlight the role of SCARF1 involvement in the gut microbiome and immune regulation in the context of inflammation and SLE.