Th17 immune responses contribute to the pathophysiology of aplastic anemia
Th17 immune responses contribute to the pathophysiology of aplastic anemia
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DOI：
10.1182/blood-2010-01-266098
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发表时间：
2010-11-18
期刊：
影响因子：
20.3
通讯作者：
Young, Neal S.
中科院分区：
文献类型：
--
作者：
de Latour, Regis Peffault;Visconte, Valeria;Young, Neal S.
辅助性T细胞17(Th17)的特征是产生白介素17(IL-17)并与自身免疫性疾病相关。从41例再生障碍性贫血(AA)患者外周血和7例骨髓单个核细胞中分离Th17细胞，研究Th17细胞在再生障碍性贫血(AA)中的作用。AA患者发病时CD3(+)、CD4(+)、IL-17产生T细胞的频率和总数均高于健康对照组(P分别为.0007和0.02)，且与疾病活动性相关。AA患者外周血中Th17细胞数量与外周血中CD4(+)、CD25(高)、FoxP3(+)调节性T细胞(Tregs)呈负相关。伴随着经典的Th1反应，我们在淋巴输注诱导的骨髓衰竭小鼠模型中检测到产生CD4(+)和CD8(+)IL-17的T细胞的存在。尽管抗IL-17治疗不能消除骨髓衰竭，但早期应用抗IL-17抗体可降低骨髓衰竭的严重程度，第10天时血小板(P<；.01)和骨髓细胞总数(P<；.05)显著增加。在淋巴结输注后第10天，接受抗IL-17治疗的受者Th1细胞(P<；.01)显著减少，Treg细胞(P<；.05)显著增加。Th17免疫反应参与了再生障碍性贫血的病理生理过程，尤其是在疾病进展的早期阶段。(《血色》2010；116(20)：4175-4184)
T helper type 17 (Th17) cells have been characterized based on production of interleukin-17 (IL-17) and association with autoimmune diseases. We studied the role of Th17 cells in aplastic anemia (AA) by isolating Th17 cells from patients blood (n = 41) and bone marrow (BM) mononuclear cells (n = 7). The frequency and total number of CD3(+)CD4(+)IL-17-producing T cells were increased in AA patients at presentation compared with healthy controls (P = .0007 and .02, respectively) and correlated with disease activity. There was an inverse relationship between the numbers of Th17 cells and CD4(+)CD25(high)FoxP3(+) regulatory T cells (Tregs) in the blood of AA patients. Concomitant with the classical Th1 response, we detected the presence of CD4(+) and CD8(+) IL-17-producing T cells in a mouse model of lymph node infusion-induced BM failure. Although anti-IL-17 treatment did not abrogate BM failure, early treatment with the anti-IL-17 antibody reduced the severity of BM failure with significantly higher platelet (P < .01) and total BM cell (P < .05) counts at day 10. Recipients that received anti-IL-17 treatment had significantly fewer Th1 cells (P < .01) and more Treg cells (P < .05) at day 10 after lymph node infusion. Th17 immune responses contribute to AA pathophysiology, especially at the early stage during disease progression. (Blood.2010;116(20):4175-4184)