OX40 and Regulatory Marker Alterations in Lesional and Non-Lesional Keloid Tissues

Introduction: Keloids are pathologic scars that result from abnormal wound healing processes following skin trauma, with a higher prevalence in the Black population. The pathogenesis of keloids is not fully understood, hindering effective treatment options for this highly disfiguring and distressing condition. Methods: Biopsies from lesional and non-lesional skin from keloid patients and healthy skin from age/gender/race-matched controls were collected and analyzed using RNA-sequencing, RT-qPCR, and immunohistochemistry. Spearman analysis was used to evaluate the correlations between biomarker expressions and clinical severity measurements. Results: Both keloidal lesions and non-lesional skin showed a distinct transcriptomic profile compared to healthy skin. Keloids demonstrated significant upregulation of fibrosis-related markers (e.g., COL10A1, COL11A1, and BMP1). Lesional and/or non-lesional samples showed significant upregulation of key immune biomarkers belonging to T-cells (e.g., CD2, CD3D, and CD3E), T-cell/NK-cell activation/migration (e.g., CCL19, CCR7, GZMA, GZMB, and GZMK), Th1 (e.g., OASL, MX1, CCL4), Th2 (e.g., IL4R, OX40/TNFRSF4, and OX40L/TNFSF4), and Th17/22 (e.g., S100A7, S100A8, S100A9, and CCL20). Multiple immune biomarkers expression (e.g., CCL2, CXCL1, and S100A7) in lesional and/or non-lesional skin significantly and positively correlated with keloid severity parameters (e.g., keloid size, distensibility, and number). Conclusion: Both lesional and non-lesional keloid skin show distinct upregulation of immune axes, underscoring the role of inflammation in keloid pathogenesis and pointing to potential novel therapeutic targets.