TL1A Produced by Lamina Propria Macrophages Induces Th1 and Th17 Immune Responses in Cooperation with IL-23 in Patients with Crohn's Disease
TL1A Produced by Lamina Propria Macrophages Induces Th1 and Th17 Immune Responses in Cooperation with IL-23 in Patients with Crohn's Disease
复制标题
DOI：
10.1002/ibd.21124
复制
发表时间：
2010-04-01
影响因子：
4.9
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
--
作者：
Kamada, Nobuhiko;Hisamatsu, Tadakazu;Hibi, Toshifumi
背景：肿瘤坏死因子样蛋白1A(TL1A)是肿瘤坏死因子超家族的一员，通过刺激辅助性T细胞(Th)1参与克罗恩病(CD)的发病过程。除了Th1，最近的研究重点是Th17细胞在CD发病机制中的作用。方法：采用定量逆转录聚合酶链式反应(RT-PCR法)检测正常人(NC)和CD及溃疡性结肠炎(UC)患者巨噬细胞(LP-M Phi S)固有层巨噬细胞TL1A的表达。纯化的LP CD4(+)T细胞用TL1A和/或IL-23刺激，检测干扰素-γ和白介素17水平。我们还检测了TL1A对初始CD_4(+)T细胞分化的影响。结果：我们发现LP-M Phi S是TL1A的主要产生者。CD患者LP-M Phi S的TL1a表达明显高于NC和UC患者。在共生菌刺激下，LP-M Phi S除TL1a外，还诱导产生IL-23。TL1A和IL-23协同促进LP T细胞产生干扰素-γ和IL-17，而单独使用TL1A不能诱导细胞因子的产生。结论：Lp-M Phi S表达的TL1a可能通过诱导Th1和Th17免疫，在CD的发病机制中起重要作用。IL-23对TL1A在记忆T细胞和幼稚T细胞上的这些功能有不同的调节作用。
Background: Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily and contributes to the pathogenesis of Crohn's disease (CD) by stimulating T-helper (Th) 1 cells. In addition to Th1, recent studies have focused on the role of Th17 cells in the pathogenesis of CD. Here we tried to clarify the role of TL1A in Th1 and Th17 immunity in CD.Methods: TL1A expression was assessed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) in lamina propria (LP) macrophages (LP-M phi s) from normal controls (NC) and patients with CD or ulcerative colitis (UC). Purified LP CD4(+) T cells were stimulated with TL1A and/or IL-23 and interferon gamma (IFN-gamma) and interleukin (IL)-17 levels were analyzed. We also examined the effect of TL1A on naive CD4(+) T-cell differentiation.Results: We found that LP-M phi s are a major producer of TL1A. TL1A expression was markedly enhanced in LP-M phi s from CD patients compared with NC or UC patients. IL-23, in addition to TL1A, was induced in LP-M phi s by commensal bacteria stimulation. TL1A and IL-23 synergistically promoted the production of IFN-gamma and IL-17 by LP T cells, while TL1A alone did not induce cytokine production. Furthermore, TL1A promoted Th17 differentiation from naive T cells by LP-M phi s: however, IL-23 did not show any synergistic effects on Th17 differentiation.Conclusions: TL1A expressed in LP-M phi s might play an important role in the pathogenesis of CD by inducing Th1 and Th17 immunity. IL-23 differentially regulated these functions of TL1A on memory and naive T cells.