Th17 reprogramming of T cells in systemic juvenile idiopathic arthritis
Th17 reprogramming of T cells in systemic juvenile idiopathic arthritis
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DOI：
10.1172/jci.insight.132508
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发表时间：
2020-03-26
期刊：
影响因子：
8
通讯作者：
Nigrovic, Peter A.
中科院分区：
文献类型：
--
作者：
Henderson, Lauren A.;Hoyt, Kacie J.;Nigrovic, Peter A.
全身性幼年特发性关节炎（sJIA）开始于发热、皮疹和高度全身性炎症，但通常进展为持续性无热性关节炎。这种转变的基础尚不清楚。为了评估淋巴细胞极化的作用，我们采用流式细胞术、质谱仪和RNA测序对急性和慢性sJIA患者的T细胞进行了鉴定。急性和慢性sJIA均具有在健康对照组或非系统性JIA儿童中不常见的活化T细胞群扩大。在急性sJIA中，T细胞表达IL-17 A和反映Th 17极化的基因表达特征。在慢性sJIA中，在T效应细胞（Tefs）中鉴定了Th 17转录特征，尽管IL-17 A在蛋白水平的表达仍然罕见。在对IL-1阻断有反应的患者中，Th 17极化被消除。这些发现确定了sJIA中不断变化的Th 17极化，该极化始于Tregs并发展为Teff，这可能反映了细胞因子环境的影响，并与疾病发病机制的双相模型一致。结果支持T细胞作为sJIA的潜在治疗靶点。
Systemic juvenile idiopathic arthritis (sJIA) begins with fever, rash, and high-grade systemic inflammation but commonly progresses to a persistent afebrile arthritis. The basis for this transition is unknown. To evaluate a role for lymphocyte polarization, we characterized T cells from patients with acute and chronic sJIA using flow cytometry, mass cytometry, and RNA sequencing. Acute and chronic sJIA each featured an expanded population of activated Tregs uncommon in healthy controls or in children with nonsystemic JIA. In acute sJIA, Tregs expressed IL-17A and a gene expression signature reflecting Th17 polarization. In chronic sJIA, the Th17 transcriptional signature was identified in T effector cells (Teffs), although expression of IL-17A at the protein level remained rare. Th17 polarization was abrogated in patients responding to IL-1 blockade. These findings identify evolving Th17 polarization in sJIA that begins in Tregs and progresses to Teffs, likely reflecting the impact of the cytokine milieu and consistent with a biphasic model of disease pathogenesis. The results support T cells as a potential treatment target in sJIA.