Interleukin 34: a new modulator of human and experimental inflammatory bowel disease.
Interleukin 34: a new modulator of human and experimental inflammatory bowel disease.
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DOI：
10.1042/cs20150176
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Boström EA
中科院分区：
文献类型：
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作者：
Zwicker S;Martinez GL;Bosma M;Gerling M;Clark R;Majster M;Söderman J;Almer S;Boström EA
IBD（炎症性肠病）是肠道的慢性炎症性病症，其中CD（克罗恩病）和UC（溃疡性结肠炎）代表两种主要形式。巨噬细胞在IBD发病机制中起核心作用，并在体内平衡和炎症中受主要分化因子如CSF-1（集落刺激因子1）的调节。IL（白细胞介素）-34最近被发现作为CSF-1 R（CSF-1受体）的第二配体。然而，IL-34在IBD中的表达和参与仍然未知。在本论文中，我们研究了IL 34，CSF 1和它们的共享受体CSF 1 R在正常人回肠和结肠，在CD和UC患者的炎症和非炎症组织中，以及在实验性结肠炎的小鼠模型中的表达。我们发现IL 34和CSF 1在回肠和结肠中有不同的表达模式，IL 34在回肠中较高，而CSF 1在结肠中较高。此外，在IBD患者和实验性结肠炎中，IL 34和CSF 1的表达随着炎症而增加。在人类中，固有层和肠上皮细胞的浸润细胞表达IL-34，TNF-α（肿瘤坏死因子α）通过NF-κB（核因子κB）途径调节肠上皮细胞中的IL-34表达。这些数据证明了IL-34在回肠和结肠中的表达模式，并表明IL-34是IBD中炎症的新调节剂。由肠上皮细胞产生的巨噬细胞分化因子白细胞介素-34在炎症性肠病患者中上调，可能是肠道炎症的新调节剂。
IBD (inflammatory bowel disease), where CD (Crohn's disease) and UC (ulcerative colitis) represent the two main forms, are chronic inflammatory conditions of the intestine. Macrophages play a central role in IBD pathogenesis and are regulated by major differentiation factors such as CSF-1 (colony-stimulating factor 1) in homoeostasis and inflammation. IL (interleukin)-34 has recently been discovered as a second ligand for CSF-1R (CSF-1 receptor). However, expression and involvement of IL-34 in IBD remain unknown. In the present paper, we investigated the expression of IL34, CSF1 and their shared receptor CSF1R in normal human ileum and colon, in inflamed and non-inflamed tissues of CD and UC patients, and in a mouse model of experimental colitis. We found distinct expression patterns of IL34 and CSF1 in ileum and colon, with higher IL34 in ileum and, in contrast, higher CSF1 in colon. Furthermore, IL34 and CSF1 expression was increased with inflammation in IBD patients and in experimental colitis. In humans, infiltrating cells of the lamina propria and intestinal epithelial cells expressed IL-34, and TNF-α (tumour necrosis factor α) regulated IL-34 expression in intestinal epithelial cells through the NF-κB (nuclear factor κB) pathway. These data demonstrate the expression pattern of IL-34 in ileum and colon and suggest IL-34 as a new modulator of inflammation in IBD. The macrophage differentiation factor interleukin-34, produced by intestinal epithelial cells, is up-regulated in patients with inflammatory bowel disease, and may be a novel modulator of intestinal inflammation.