Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis
Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis
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DOI：
10.1007/s00535-014-0977-4
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发表时间：
2015-04-01
影响因子：
6.3
通讯作者：
Okazaki, Kazuichi
中科院分区：
文献类型：
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作者：
Fukui, Yuri;Uchida, Kazushige;Okazaki, Kazuichi
血清免疫球蛋白G4(IgG4)水平升高和IgG4阳性浆细胞浸润是1型自身免疫性胰腺炎(AIP)的特征。目前尚不清楚先天免疫是否是1型AIP的原因；微生物感染可能参与了其发病机制。为了阐明1型AIP的发病机制，我们研究了9例1型AIP患者的Toll样受体(TLRs)，并以10例酒精性慢性胰腺炎(ACP)和3例神经内分泌肿瘤(NET)非肿瘤性病变的标本为对照。用抗TLR1-11抗体进行免疫组织化学染色，计数TLR1-11阳性细胞数。在1型急性胰腺炎患者胰腺组织中，TLR7(8.815+/-A 1.755)、TLR8(3.852+/-A 1.489)和TLR10(3.852+/-A 0.921)高表达。仅TLR7/单核细胞比率在1型急性胰腺炎(0.053+/-A 0.012)显著高于急性胰腺炎(0.007+/-A 0.004；P<0.01)和非肿瘤性病变(0.000+/-A 0.000；P<0.01)。1型AIP患者CD163/TLR7比值(0.789+/-A 0.031)显著高于CD123/TLR7比值(0.034+/-A 0.006；P<0.001)和CD20/TLR7比值(0.029+/-A 0.010；P<0.001)，TLR7可能是参与1型AIP发生发展的关键模式识别受体。
High serum immunoglobulin G4 (IgG4) levels and IgG4-positive plasma cell infiltration are characteristic of type 1 autoimmune pancreatitis (AIP). It is unclear whether innate immunity is a cause of type 1 AIP; the possible involvement of microbial infection has been suggested in its pathogenesis. To clarify the pathogenesis of type 1 AIP, we investigated Toll-like receptors (TLRs) in type 1 AIP patients.We studied nine cases of type 1 AIP with ten cases of alcoholic chronic pancreatitis (ACP) and three of the samples from non-tumorous lesion of neuroendocrine tumor (NET) as control subjects. We counted the number of TLR1-11-positive cells immunohistochemically stained with anti-TLR1-11 antibodies. To identify TLR-positive cells in pancreata from type 1 AIP patients, we used a double-immunofluorescence method and counted the numbers of identifiable CD68-, CD163-, CD123-, and CD20-positive cells.In type 1 AIP, TLR7 (8.815 +/- A 1.755), TLR8 (3.852 +/- A 1.489), and TLR10 (3.852 +/- A 0.921) were highly expressed. Only the ratio of TLR7 per monocyte was significantly higher in type 1 AIP (0.053 +/- A 0.012) than in ACP (0.007 +/- A 0.004; p < 0.01) and non-tumorous lesion of NET (0.000 +/- A 0.000; p < 0.01). In type 1 AIP, the CD163 to TLR7 ratio (0.789 +/- A 0.031) was significantly higher both than that of CD123 to TLR7 ratio (0.034 +/- A 0.006; p < 0.001) and CD20 to TLR7 ratio (0.029 +/- A 0.010; p < 0.001).TLR7 might be key pattern-recognition receptors involved in the development of type 1 AIP.