Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Department of Anatomy, Histology and Physiology, Faculty of Animal Science and Veterinary Medicine, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh.
Front Immunol. 2020 Dec 15;11:595672. doi: 10.3389/fimmu.2020.595672. eCollection 2020.
Lupus nephritis (LN) is a common complication in young patients and the most predominant cause of glomerulonephritis. Infiltrating immune cells and presence of immunocomplexes in the kidney are hallmarks of LN, which is closely associated with renal lesions (RLs). However, their regulatory mechanism in the kidney remains unclear, which is valuable for prevention of RL development. Here, we show the development of vasculature-associated lymphoid tissue (VALT) in LN, which is related to renal inflammatory cytokines, indicating that VALT is a unique tertiary lymphoid tissue. Transcriptomic analysis revealed different chemokines and costimulatory molecules for VALT induction and organization. Vascular and perivascular structures showed lymphoid tissue organization through lymphorganogenic chemokine production. Transcriptional profile and intracellular interaction also demonstrated antigen presentation, lymphocyte activity, clonal expansion, follicular, and germinal center activity in VALT. Importantly, VALT size was correlated with infiltrating immune cells in kidney and RLs, indicating its direct correlation with the development of RLs. In addition, dexamethasone administration reduced VALT size. Therefore, inhibition of VALT formation would be a novel therapeutic strategy against LN.
狼疮性肾炎（LN）是年轻患者的常见并发症，也是肾小球肾炎的最主要病因。免疫细胞浸润和免疫复合物在肾脏中的存在是 LN 的特征，与肾脏病变（RLs）密切相关。然而，它们在肾脏中的调节机制尚不清楚，这对于预防 RL 的发展具有重要价值。在这里，我们展示了 LN 中与脉管系统相关的淋巴组织（VALT）的发育，这与肾脏炎症细胞因子有关，表明 VALT 是一种独特的三级淋巴组织。转录组分析揭示了不同的趋化因子和共刺激分子用于 VALT 的诱导和组织。血管和血管周围结构通过淋巴器官生成趋化因子的产生显示出淋巴组织的组织。转录谱和细胞内相互作用还表明 VALT 中的抗原呈递、淋巴细胞活性、克隆扩增、滤泡和生发中心活性。重要的是，VALT 的大小与肾脏和 RL 中的浸润免疫细胞相关，表明其与 RL 的发展直接相关。此外，地塞米松的给药减少了 VALT 的大小。因此，抑制 VALT 的形成将是治疗 LN 的一种新的治疗策略。
