Potential peptide drug with LCCL core motif differentiating M1 macrophage

Cochlin, encoded by the COCH gene, mediates innate immunity against bacterial infections by segregating pathogens and recruiting immune cells through its N-terminal LCCL domain. This domain is cleaved and secreted to attract macrophages and neutrophils, but its core motif has remained unclear. Here, we identified a 62–amino acid core LCCL (cLCCL) containing conserved structural elements. RNA-seq in RAW264.7 cells showed that both LCCL and cLCCL peptides induced M1 polarization, with upregulation of TICAM2, CD40, and CD86. Thus, cLCCL drives pro-inflammatory macrophage polarization and represents a promising candidate for antibacterial peptide therapeutics