MSU crystal deposition contributes to inflammation and immune responses in gout remission
MSU crystal deposition contributes to inflammation and immune responses in gout remission
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DOI：
10.1016/j.celrep.2023.113139
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发表时间：
2023-09-26
期刊：
影响因子：
8.8
通讯作者：
Peng，Ai
中科院分区：
文献类型：
--
作者：
Gu，Hongchen;Yu，Hanqing;Peng，Ai
作为痛风的一个显著特征，尿酸盐（MSU）晶体沉积诱导痛风发作，但其对痛风缓解期免疫炎症的影响尚不清楚。使用单细胞RNA测序（scRNA-seq），我们的特点转录谱的外周血单核细胞（PBMC）之间的临界缓解痛风，晚期缓解痛风，和正常对照。我们发现，在痛风缓解与MSU晶体沉积在中间和先进的阶段，证明了激活的炎症途径，加强炎症细胞间的相互作用，并提高花生四烯酸代谢活性的全身炎症。我们还发现，在晚期痛风患者中，HLA-DQA 1高水平的经典单核细胞和PTGS 2高水平的单核细胞增加，在临界期和晚期痛风患者中，过度活化的CD 8 +T细胞亚型增加。此外，破骨细胞分化途径在晚期痛风的单核细胞、T细胞和B细胞中显著富集。总体而言，我们证明了全身炎症和独特的免疫反应在痛风缓解与MSU晶体沉积，允许进一步探索的潜在机制和临床意义，从临界转换到先进的阶段。
As a prominent feature of gout, monosodium urate (MSU) crystal deposition induces gout flares, but its impact on immune inflammation in gout remission remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterize the transcription profiling of peripheral blood mononuclear cells (PBMCs) among intercritical remission gout, advanced remission gout, and normal controls. We find systemic inflammation in gout remission with MSU crystal deposition at the intercritical and advanced stages, evidenced by activated inflammatory pathways, strengthened inflammatory cell-cell interactions, and elevated arachidonic acid metabolic activity. We also find increasedHLA-DQA1highclassic monocytes andPTGS2highmonocytes in advanced gout and overactivated CD8+T cell subtypes in intercritical and advanced gout. Additionally, the osteoclast differentiation pathway is significantly enriched in monocytes, T cells, and B cells from advanced gout. Overall, we demonstrate systemic inflammation and distinctive immune responses in gout remission with MSU crystal deposition, allowing further exploration of the underlying mechanism and clinical significance in conversion from intercritical to advanced stage.