Duan Shumin, Li Qionghua, Wang Fei, Kuang Wenjing, Dong Yunmei, Liu Dan, Wang Jiongke, Li Wei, Chen Qianming, Zeng Xin, Li Taiwen
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Department of Dermatology, Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
J Immunol. 2024 Feb 1;212(3):375-388. doi: 10.4049/jimmunol.2300312.
The etiology and pathogenesis of pemphigus vulgaris (PV) entail intricate interactions between immune cells and epithelial cells. However, the specific subtypes of immune cells involved in PV, along with their respective roles, remain elusive. Likewise, the precise functions and mechanisms by which glucocorticoids affect cell types within the disease context require further elucidation. To address these knowledge gaps, we performed 5' single-cell RNA sequencing, combined with V(D)J enrichment on buccal mucosal lesions and peripheral blood samples from treatment-naive patients with PV, in conjunction with post-treatment peripheral blood samples obtained after oral prednisone treatment. Our findings suggest that the IL-1α signaling pathway, myeloid APCs, inflammatory CD8+ resident memory T cells, and dysfunctional CD4+ regulatory T cells are involved in the pathogenesis of PV. Part of these findings were validated by immunohistochemical assays and multiplex immunofluorescence assays. Furthermore, our results highlight the significant impact of prednisone treatment on monocytes and mucosal-associated invariant T cells while revealing a limited effect on CD4+ regulatory T cells. Additionally, we present the CDR3 amino acid sequence of BCR related to PV disease and investigate the characteristics of TCR/BCR clonotypes. In conclusion, our study provides a comprehensive understanding of PV, particularly focusing on the mucosal-dominant type, and sheds light on the effects of glucocorticoids within the PV context. These insights hold promise for the development of new therapeutic strategies in this autoimmune disorder.
寻常型天疱疮（PV）的病因和发病机制涉及免疫细胞与上皮细胞之间复杂的相互作用。然而，参与PV的免疫细胞的具体亚型及其各自的作用仍不清楚。同样，糖皮质激素在疾病背景下影响细胞类型的精确功能和机制需要进一步阐明。为了填补这些知识空白，我们对未经治疗的PV患者的颊黏膜病变和外周血样本进行了5'单细胞RNA测序，并结合V(D)J富集，同时对口服泼尼松治疗后的外周血样本进行了分析。我们的研究结果表明，IL-1α信号通路、髓样抗原呈递细胞、炎性CD8 + 组织驻留记忆T细胞和功能失调的CD4 + 调节性T细胞参与了PV的发病机制。这些发现的一部分通过免疫组织化学检测和多重免疫荧光检测得到了验证。此外，我们的结果突出了泼尼松治疗对单核细胞和黏膜相关恒定T细胞的显著影响，同时揭示了对CD4 + 调节性T细胞的影响有限。此外，我们展示了与PV疾病相关的BCR的CDR3氨基酸序列，并研究了TCR/BCR克隆型的特征。总之，我们的研究提供了对PV的全面理解，特别是聚焦于黏膜主导型，并阐明了糖皮质激素在PV背景下的作用。这些见解为这种自身免疫性疾病新治疗策略的开发带来了希望。
