DNA–protein networks in bullous pemphigoid: The emerging role of extracellular traps

Abstract

Bullous pemphigoid (BP) is an inflammatory autoimmune skin disease primarily caused by anti-BP180 autoantibodies. Recent investigations have uncovered the critical involvement of extracellular traps (ETs) in BP pathogenesis. These web-like structures released by leukocytes are mainly composed of DNA, histones, and granular proteins. Both neutrophil ETs (NETs) and eosinophil ETs (EETs) are found at relatively high levels in BP lesions, particularly near the dermal–epidermal junction (DEJ). These ETs significantly influence immune cell differentiation within the BP environment. NETs promote the differentiation of B cells into CD19 ⁺ CD138 ⁺ plasma cells, leading to increased autoantibody production. Similarly, EETs drive the differentiation of T cells into follicular helper T cells and contribute to DEJ separation. DNase can block these effects by degrading the DNA structure. In addition, granular proteins within ETs, such as neutrophil elastase, eosinophil cationic protein, and eosinophil-derived neurotoxin, have been demonstrated to play critical roles in the pathogenesis of BP. In this review, we focus on the formation mechanism and structural characteristics of ETs and reveal the role of ETs in the BP.