IL-1β mediated fibroblast-neutrophil crosstalk promotes inflammatory environment in skin lesions of SLE

Systemic lupus erythematosus (SLE) is characterized by immune dysregulation, with neutrophil infiltration in skin lesions contributing to inflammation and disease progression. However, the interaction between fibroblasts and neutrophils in SLE skin lesions has not been fully explored. Using single-cell RNA sequencing, we identified a unique CXCL1⁺ fibroblast subset in SLE lesions. We found that CXCL1⁺ fibroblasts recruit and activate neutrophils, increasing the production of inflammatory mediators, reactive oxygen species, and neutrophil extracellular traps. These fibroblasts also facilitated the transition of neutrophils to a low-density phenotype. Notably, these fibroblasts delayed neutrophil apoptosis, extending their survival and amplifying inflammation. Serum amyloid A1, secreted by CXCL1⁺ fibroblasts, emerged as a key activator of neutrophils. Activated neutrophils, in turn, secreted IL-1β to induce CXCL1⁺ fibroblasts differentiation via activating the NF-κB pathway. In conclusion, our findings reveal that IL-1β-induced CXCL1⁺ fibroblasts significantly modulate pro-inflammatory neutrophils, underscoring the critical crosstalk between fibroblasts and neutrophils in SLE pathogenesis.