Table_1_Vasculature-Associated Lymphoid Tissue: A Unique Tertiary Lymphoid Tissue Correlates With Renal Lesions in Lupus Nephritis Mouse Model.docx

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）是年轻患者常见的并发症，也是肾小球肾炎的最主要病因。浸润性免疫细胞和免疫复合物的存在是LN的标志性特征，与肾脏病变（RLs）密切相关。然而，它们在肾脏中的调控机制尚不明确，这对于预防RLs的发展具有重要意义。在本研究中，我们展示了LN中血管相关淋巴组织（VALT）的发展，该组织与肾脏炎症细胞因子相关，表明VALT是一种独特的三级淋巴组织。转录组分析揭示了VALT诱导和组织过程中不同的趋化因子和共刺激分子。血管和血管周围结构通过淋巴生成趋化因子的产生显示出淋巴组织的组织化。转录谱和细胞内相互作用还展示了VALT中的抗原呈递、淋巴细胞活性、克隆扩增、滤泡和生发中心活动。值得注意的是，VALT的大小与肾脏中浸润的免疫细胞和RLs相关，表明其与RLs的发展有直接关联。此外，地塞米松的给予可减少VALT的大小。因此，抑制VALT的形成将可能成为治疗LN的一种新型治疗策略。