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 RNA-seq profiling of RAW264.7 cells that were untreated or treated with 1ug or 10ug of LCCL for 6 hours or 24 hours.

由COCH基因编码的耳蜗蛋白（Cochlin）可通过其N端LCCL结构域（LCCL domain）分离病原体并招募免疫细胞，介导抗细菌感染的固有免疫应答。该结构域经剪切分泌后可趋化巨噬细胞与中性粒细胞，但其核心基序迄今尚未明确。本研究鉴定得到一段包含保守结构元件的62氨基酸核心LCCL片段（cLCCL）。对RAW264.7细胞的RNA测序分析显示，LCCL与cLCCL肽段均可诱导巨噬细胞向M1型极化，并上调TICAM2、CD40及CD86的基因表达。综上，cLCCL可驱动促炎型巨噬细胞极化，是极具潜力的抗菌肽治疗候选分子。本研究的RNA测序数据集涵盖未处理的RAW264.7细胞，以及经1μg或10μg LCCL肽段分别处理6小时、24小时的RAW264.7细胞。