Immunophenotypic characteristics of Langhans giant cells and the role of CCR7 in their formation

Langhans giant cells (LGCs) play a crucial role in granulomatous diseases, yet their unique molecular characteristics and formation mechanisms remain unclear. In this study, we aimed to systematically characterize the molecular features of LGCs and reveal the role of CCR7 in their formation. Mouse bone marrow-derived macrophages (BMDMs) were induced and filtrated to obtain purified LGCs in vitro. RNA sequencing and bioinformatics analysis identified over 3000 differentially expressed genes (DEGs) between LGCs and M0 macrophages, with significant enrichment in cytokine-mediated signaling, extracellular matrix, and cytokine receptor activity. Immunophenotypic analysis revealed elevated expression of antigen-presenting molecules (CD80, CD86, CD40) in LGCs, particularly after Mycobacterium marinum infection. Further investigations demonstrated that CCR7 expression, along with its ligand CCL19, was significantly upregulated at both RNA and protein levels in LGCs compared to M0 macrophages. Small interfering RNA (siRNA) targeting CCR7 led to a marked reduction in LGC formation. Immunohistochemistry confirmed elevated CCR7 expression in LGCs from granuloma model mice and patients with mycobacterial infections. In conclusion, LGCs exhibit distinct molecular characteristics compared to M0 macrophages, with elevated antigen-presenting molecule expression and CCR7 involvement. CCR7 plays a crucial role in LGC formation, providing novel insights into granulomatous disease pathogenesis and potential therapeutic targets.