Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
J Gastroenterol. 2015 Apr;50(4):435-44. doi: 10.1007/s00535-014-0977-4. Epub 2014 Jul 9.
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 ± 1.755), TLR8 (3.852 ± 1.489), and TLR10 (3.852 ± 0.921) were highly expressed. Only the ratio of TLR7 per monocyte was significantly higher in type 1 AIP (0.053 ± 0.012) than in ACP (0.007 ± 0.004; p < 0.01) and non-tumorous lesion of NET (0.000 ± 0.000; p < 0.01). In type 1 AIP, the CD163 to TLR7 ratio (0.789 ± 0.031) was significantly higher both than that of CD123 to TLR7 ratio (0.034 ± 0.006; p < 0.001) and CD20 to TLR7 ratio (0.029 ± 0.010; p < 0.001).
TLR7 might be key pattern-recognition receptors involved in the development of type 1 AIP.
高血清免疫球蛋白 G4（IgG4）水平和 IgG4 阳性浆细胞浸润是 1 型自身免疫性胰腺炎（AIP）的特征。先天免疫是否是 1 型 AIP 的病因尚不清楚；其发病机制中可能涉及微生物感染。为了阐明 1 型 AIP 的发病机制，我们研究了 1 型 AIP 患者的 Toll 样受体（TLR）。
我们研究了 9 例 1 型 AIP 患者和 10 例酒精性慢性胰腺炎（ACP）患者及 3 例神经内分泌肿瘤（NET）非肿瘤病变的样本。我们用抗 TLR1-11 抗体通过免疫组化染色计数 TLR1-11 阳性细胞的数量。为了鉴定 1 型 AIP 患者胰腺中的 TLR 阳性细胞，我们使用双免疫荧光法计数可识别的 CD68、CD163、CD123 和 CD20 阳性细胞的数量。
在 1 型 AIP 中，TLR7（8.815 ± 1.755）、TLR8（3.852 ± 1.489）和 TLR10（3.852 ± 0.921）表达水平较高。仅 1 型 AIP 中 TLR7 与单核细胞的比值（0.053 ± 0.012）显著高于 ACP（0.007 ± 0.004；p < 0.01）和 NET 非肿瘤病变（0.000 ± 0.000；p < 0.01）。在 1 型 AIP 中，CD163 与 TLR7 的比值（0.789 ± 0.031）明显高于 CD123 与 TLR7 的比值（0.034 ± 0.006；p < 0.001）和 CD20 与 TLR7 的比值（0.029 ± 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。
