Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis.
Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis.
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DOI：
10.1007/s00535-017-1390-6
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发表时间：
2018-03
影响因子：
6.3
通讯作者：
Okazaki K
中科院分区：
文献类型：
--
作者：
Yanagawa M;Uchida K;Ando Y;Tomiyama T;Yamaguchi T;Ikeura T;Fukui T;Nishio A;Uemura Y;Miyara T;Okamoto H;Satoi S;Okazaki K
1型自身免疫性胰腺炎（AIP）的病理生理机制尚不清楚。我们以前报道过M2巨噬细胞可能在1型AIP中起重要作用。最近，据报道，嗜碱性粒细胞调节分化为M2巨噬细胞。在这项研究中，我们调查了1型AIP患者胰腺组织和外周血中的嗜碱性粒细胞。通过免疫组织化学方法，我们研究了13例1型AIP患者胰腺组织中的嗜碱性粒细胞，并检测了这些细胞的Toll样受体（TLR）表达。此外，我们还从27名健康受试者、40名1型AIP患者、8名酒精性慢性胰腺炎患者、10名支气管哮喘患者和10名特应性皮炎患者中采集外周血样本，并通过用TLR 1 -9配体刺激嗜碱性粒细胞来分析嗜碱性粒细胞的活化。我们还比较了组织和血液样本中嗜碱性粒细胞的TLR表达。13例1型AIP患者中有10例胰腺组织中检测到嗜碱性粒细胞。流式细胞仪检测结果显示，1型AIP和异位性皮炎患者经TLR 4激活的嗜碱性粒细胞比例（9.875 ± 1.148%，11.768 ± 1.899%）明显高于健康对照组（5.051 ± 0.730%，P < 0.05）。TLR 2刺激激活的嗜碱性粒细胞水平在7例1型AIP病例中较高。此外，刺激胰腺中嗜碱性粒细胞表达的TLR 2和/或TLR 4可激活外周血中的嗜碱性粒细胞。通过TLR信号激活的嗜碱性粒细胞可能在1型AIP的病理生理学中起重要作用。
Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP. By using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells. Additionally, we obtained peripheral blood samples from 27 healthy subjects, 40 patients with type 1 AIP, 8 patients with alcoholic chronic pancreatitis, 10 patients with bronchial asthma, and 10 patients with atopic dermatitis, and analyzed activation of basophils by stimulating them with ligands of TLR1–9. We also compared TLR expression in basophils from the tissue and blood samples. Basophils were detected in pancreatic tissues from 10 of 13 patients with type 1 AIP. Flow cytometric analysis revealed that the ratios of basophils activated by TLR4 stimulation in type 1 AIP (9.875 ± 1.148%) and atopic dermatitis (11.768 ± 1.899%) were significantly higher than those in healthy subjects (5.051 ± 0.730%; P < 0.05). Levels of basophils activated by TLR2 stimulation were higher in seven type 1 AIP cases. Furthermore, stimulation of TLR2 and/or TLR4, which were expressed by basophils in pancreas, activated basophils in peripheral blood. Basophils activated via TLR signaling may play an important role in the pathophysiology of type 1 AIP.
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