IL-15 is highly expressed in inflammatory bowel disease and regulates local T cell-dependent cytokine production
IL-15 is highly expressed in inflammatory bowel disease and regulates local T cell-dependent cytokine production
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DOI：
10.4049/jimmunol.164.7.3608
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发表时间：
2000-04-01
影响因子：
4.4
通讯作者：
Ceuppens, JL
中科院分区：
文献类型：
--
作者：
Liu, ZJ;Geboes, K;Ceuppens, JL
IL-15具有与IL-2相似的生物学活性，但序列上没有明显的同源性，它能诱导T细胞向炎症部位募集、T细胞增殖、细胞因子的产生和凋亡的挽救。本研究旨在探讨IL-15在炎症性肠病（IBD）中的表达及其对促炎细胞因子产生的影响。免疫组织化学显示IBD患者炎症粘膜中巨噬细胞局部产生IL-15。当用LPS或IFN-γ刺激时，来自这些患者而不是来自对照的分离的固有层单核细胞产生IL-15。此外，与对照相比，来自IBD患者的固有层T细胞（LP-T）对IL-15的响应更强，并且单独的IL-15而没有初级T细胞刺激诱导分离的IBD LP-T细胞产生IFN-γ和TNF。尤其是克罗恩病患者的LP-T细胞。IBD患者的LP-T细胞在共培养体系中可诱导单核细胞产生CD 40-CD 40配体（CD 40 L）相互作用依赖的TNF和IL-12。LP-T细胞的这种能力通过在IL-15中预孵育而强烈增强，并且是在IL-15中培养后更高的CD 40 L表达的结果。这些数据表明IL-15在IBD中的发炎粘膜中过表达，并且IL-15通过T细胞和巨噬细胞两者增强局部T细胞活化、增殖和促炎细胞因子产生。后者通过CD 40-CD 40 L相互作用依赖性机制。针对IL-15的治疗可能在IBD中具有治疗潜力。
IL-15 shares biological activities but no significant sequence homology with IL-2, It induces T cell recruitment to sites of inflammation, T cell proliferation, and cytokine production and rescue from apoptosis, The aim of this study was to investigate expression of IL-15 and its effects on proinflammatory cytokine production in inflammatory bowel disease (IBD). Immunohistochemistry demonstrated local IL-15 production by macrophages in inflamed mucosa from IBD patients. Isolated lamina propria mononuclear cells from these patients but not from controls produced IL-15 when stimulated with LPS or IFN-gamma, Moreover, lamina propria T cells (LP-T) from IBD patients were more responsive to IL-15 as compared with controls, and IL-15 alone without a primary T cell stimulus induced IFN-gamma and TNF production by isolated IBD LP-T cells, especially by LP-T cells from patients with Crohn's disease. LP-T cells from IBD patients could induce CD40-CD40 ligand (CD40L) interaction-dependent TNF and IL-12 production by monocytes in a coculture system. This capacity of LP-T cells was strongly enhanced by preincubation in IL-15 and was the result of higher CD40L expression after culture in IL-15, These data indicate that IL-15 is overexpressed in the inflamed mucosa in IBD and that IL-15 enhances local T cell activation, proliferation, and proinflammatory cytokine production by both T cells and macrophages, the latter via a CD40-CD40L interaction dependent mechanism. Treatment directed against IL-15 may have therapeutic potential in IBD.