异位淋巴结构（ELS）是病理情况下局部免疫细胞聚集所形成的团块状结构，存在于多种自身免疫病的靶器官，如类风关、干燥综合征等。ELS可提供特定的场所使自身反应性B细胞成熟、活化，并产生自身抗体，参与或加剧局部免疫病理反应。天疱疮是一危重的自身免疫性大疱病，局部皮损的加重和复发机制尚不明了。本课题组在临床上发现针对皮损的外用治疗具有良好的疗效，降低长期大剂量系统使用糖皮质激素的副作用；在实验中发现天疱疮皮损局部存在免疫活性细胞，形成ELS；自身反应性B细胞可活化产生特异性自身抗体；且多个相关长链非编码RNA（lncRNA）较正常有差异性表达。本研究将在前期工作的基础上，探索天疱疮皮损ELS的形成及自身反应性B细胞成熟活化的过程，筛选差异表达的lncRNAs，明确其具体调控机制。通过本研究，将丰富天疱疮皮损的形成机制，夯实天疱疮外用疗法的理论基础，进一步研发新的生物学诊断标记及新的靶向治疗药物。

Ectopic lymphoid structure (ELS) is a localized cluster or structure of aggregated immune cells in chronic inflammation, which exists in a variety of target organs of autoimmune diseases, such as rheumatoid arthritis and Sjogren's syndrome. ELS could provide specific sites for autoreactive B cells to be mature, be activated, and further to produce autoantibodies, which contributes to exacerbate local immune pathological reactions. Pemphigus is a severe autoimmune bullous skin disease, and the mechanism that how local skin lesions form is not clear. Clinically, we find that the topical therapy on skin lesions is effective, and could reduce the side effects of the long-term systemic application of glucocorticoid. In the previous study we also find that pemphigus lesions harbor immune cells, which underlie ELS; autoreactive B cells could be differentiated and produce specific autoantibodies; and multiple associated long chain noncoding RNAs (lncRNAs) showed differentially expression. In this study, we will explore the process of local ELS formation and autoreactive B cell maturation in pemphigus lesions, and screen the differentially expressed lncRNAs, and elucidate the specific regulation mechanism. Our study will enrich the mechanisms of pemphigus lesions, lay a foundation of experimental basis of topical therapy in pemphigus, and help to further explore new biology diagnostic markers and new targeted therapy of pemphigus.