Nara K, Kurokawa M S, Chiba S, Yoshikawa H, Tsukikawa S, Matsuda T, Suzuki N
Department of Immunology, St Marianna University School of Medicine, Kawasaki, Japan.
Clin Exp Immunol. 2008 May;152(2):245-51. doi: 10.1111/j.1365-2249.2008.03626.x. Epub 2008 Mar 10.
The involvement of excessive T helper 1 (Th1) cell functions in the pathogenesis of Behçet's disease (BD) has been reported. We therefore studied Toll-like receptor (TLR)-expressing cells, which play important roles in innate immunity in patients with BD. Peripheral blood mononuclear cells (PBMC) of BD and healthy controls, and tissue specimens of intestinal BD and Crohn's disease (CD) were analysed for messenger RNA (mRNA) and protein expressions by reverse transcription-polymerase chain reaction and immunostaining respectively. PBMC of BD expressed TLR-2 and TLR-4 mRNA almost comparable with healthy controls. Intestinal lesions of BD expressed TLR-2 and TLR-4 mRNA consistently. In contrast, TLR-4 mRNA was expressed preferentially and TLR-2 mRNA was expressed less frequently in CD lesions. In intestinal samples of BD, TLR-2 and TLR-4 mRNA were detected in ileocaecal ulcer lesions, but not in unaffected sites of the same sample, indicating the association of the TLR expression with the disease manifestation of intestinal BD. TLR-2-expressing cells which were simultaneously cluster of distribution (CD)68-positive produced interleukin (IL)-12 in the lesions, indicating the participation of TLR-2-expressing cells in the Th1 skewed responses in vivo. As a possible ligand of TLR-2, in BD self-heat shock protein 60 was expressed in peripheral blood lymphocytes and intestinal tissues. Collectively, TLR-2-expressing cells as well as TLR-4-expressing cells accumulated in the intestinal lesions of BD. IL-12 produced by TLR-2-expressing cells may contribute to the induction of Th1-dominant immune responses in intestinal BD.
已有报道称，辅助性T细胞1（Th1）功能亢进参与白塞病（BD）的发病机制。因此，我们研究了在BD患者固有免疫中起重要作用的Toll样受体（TLR）表达细胞。分别采用逆转录-聚合酶链反应和免疫染色法，分析了BD患者和健康对照者的外周血单个核细胞（PBMC）以及肠道BD和克罗恩病（CD）的组织标本中的信使核糖核酸（mRNA）和蛋白表达。BD患者的PBMC表达的TLR-2和TLR-4 mRNA与健康对照者几乎相当。BD的肠道病变持续表达TLR-2和TLR-4 mRNA。相比之下，CD病变中优先表达TLR-4 mRNA，而TLR-2 mRNA表达较少。在BD的肠道样本中，在回盲部溃疡病变中检测到TLR-2和TLR-4 mRNA，但在同一样本的未受影响部位未检测到，这表明TLR表达与肠道BD的疾病表现相关。同时表达分布簇（CD）68阳性的TLR-2表达细胞在病变中产生白细胞介素（IL）-12，表明表达TLR-2的细胞参与了体内Th1偏向性反应。作为TLR-2的一种可能配体，在BD中，自身热休克蛋白60在外周血淋巴细胞和肠道组织中表达。总体而言，表达TLR-2的细胞以及表达TLR-4的细胞在BD的肠道病变中积聚。表达TLR-2的细胞产生的IL-12可能有助于在肠道BD中诱导以Th1为主导的免疫反应。
