美国纽约大学Catherine P. Lu小组发现，皮肤免疫-间充质相互作用在三级淋巴结构中，促进化脓性汗腺炎的自身免疫发病机制。2024年12月10日，《免疫》杂志在线发表了这项成果。

研究人员检测了人类化脓性汗腺炎（HS）病变中的免疫微环境。多组学分析和多重成像技术揭示了HS隧道附近的三级淋巴结构（TLS）。这些TLS富含增殖性T细胞，包括滤泡辅助T细胞（Tfh）、调节性T细胞（Treg）和致病性T细胞（IL17A+和IFNG+），同时伴随着对角质形成细胞产生反应的抗体的浆细胞的广泛克隆扩展。HS成纤维细胞在免疫细胞因子的刺激下表达CXCL13或CCL19。

通过使用微流控系统模拟芯片上的TLS，研究人员发现，HS成纤维细胞通过肿瘤坏死因子α（TNF-α）-CXCL13和TNF-α-CCL19反馈回路，分别与B细胞和T细胞协同作用，关键性地调控了淋巴细胞聚集，早期的TNF-α封闭抑制了聚集的启动。

这些研究结果为皮肤中TLS的形成提供了新的见解，建议了治疗HS的途径，并揭示了可能适用于其他自身免疫疾病（如克罗恩病）的机制。

据了解，HS是一种慢性、衰弱性的炎症性皮肤疾病，其特征是角化的上皮隧道深入真皮层。

附：英文原文

Title: Skin immune-mesenchymal interplay within tertiarylymphoid structures promotes autoimmune pathogenesis in hidradenitis suppurativa

Author: Wei-Wen Yu, Joy N.P. Barrett, Jie Tong, Meng-Ju Lin, Meaghan Marohn, Joseph C. Devlin, Alberto Herrera, Juliana Remark, Jamie Levine, Pei-Kang Liu, Victoria Fang, Abigail M. Zellmer, Derek A. Oldridge, E. John Wherry, Jia-Ren Lin, Jia-Yun Chen, Peter Sorger, Sandro Santagata, James G. Krueger, Kelly V. Ruggles, Fei Wang, Chang Su, Sergei B. Koralov, Jun Wang, Ernest S. Chiu, Catherine P. Lu

Issue&Volume: 2024/12/10

Abstract: Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease characterized by keratinized epithelial tunnels that grow deeply into the dermis. Here, we examined the immune microenvironment within human HS lesions. Multi-omics profiling and multiplexed imaging identified tertiary lymphoid structures (TLSs) near HS tunnels. These TLSs were enriched with proliferative T cells, including follicular helper (Tfh), regulatory (Treg), and pathogenic T cells (IL17A+ and IFNG+), alongside extensive clonal expansion of plasma cells producing antibodies reactive to keratinocytes. HS fibroblasts express CXCL13 or CCL19 in response to immune cytokines. Using a microfluidic system to mimic TLS on a chip, we found that HS fibroblasts critically orchestrated lymphocyte aggregation via tumor necrosis factor alpha (TNF-α)-CXCL13 and TNF-α-CCL19 feedback loops with B and T cells, respectively; early TNF-α blockade suppressed aggregate initiation. Our findings provide insights into TLS formation in the skin, suggest therapeutic avenues for HS, and reveal mechanisms that may apply to other autoimmune settings, including Crohn’s disease.

DOI: 10.1016/j.immuni.2024.11.010

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00525-9