Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis.
Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis.
复制标题
DOI：
10.1053/j.gastro.2010.04.006
复制
发表时间：
2010-08
期刊：
影响因子：
29.4
通讯作者：
Hogan SP
中科院分区：
文献类型：
--
作者：
Munitz A;Cole ET;Beichler A;Groschwitz K;Ahrens R;Steinbrecher K;Willson T;Han X;Denson L;Rothenberg ME;Hogan SP
先天性和适应性免疫反应由激活信号和抑制信号之间的串扰调节。抑制信号的失调可导致异常的慢性炎症性疾病，例如炎症性肠病（IBD）。关于先天性肠道免疫激活的负调节知之甚少。我们研究了抑制性受体配对免疫球蛋白样受体 B (PIR-B) 在调节先天肠道免疫中巨噬细胞功能中的作用。我们检查了 Pirb-/- 和野生型 (WT) 小鼠对右旋糖酐硫酸钠 (DSS) 诱导的结肠炎的敏感性。我们评估了大肠杆菌刺激后 Pirb-/- 和 WT 巨噬细胞中促炎细胞因子的释放以及 MAPK 和 NFκB 的激活。进行巨噬细胞转移实验以确定 PIR-B 在 DSS 诱导的结肠炎巨噬细胞功能负调节中的作用。我们还评估了健康个体（对照）和 IBD 患者的结肠活检样本中 PIR-B 人类同源物（ILT-2 和 ILT-3）的表达。 Pirb-/- 小鼠对 DSS 诱导的结肠炎的易感性增加。体外分析表明，细菌激活后，Pirb-/- 巨噬细胞中促炎细胞因子（IL-6、IL-1β 和 TNF-α）的产生增加以及 MAPK 和 NFκB 的激活。将骨髓来源的 Pirb-/- 巨噬细胞过继转移至 WT 小鼠体内足以增加疾病易感性。 ILT-2 和 ILT-3 在患者和对照结肠活检样本中的 CD68+ 和 CD68- 单核细胞以及肠上皮上表达。 PIR-B 负向调节巨噬细胞功能，以响应病原菌和慢性肠道炎症反应。 PIR-B 等抑制性受体可作为 IBD 患者的治疗靶点。
Innate and adaptive immune responses are regulated by crosstalk between activation and inhibitory signals. Dysregulation of the inhibitory signal can lead to aberrant chronic inflammatory diseases such as the inflammatory bowel diseases (IBD). Little is known about negative regulation of innate intestinal immune activation. We examined the role of the inhibitory receptor paired immunoglobulin-like receptor B (PIR-B) in the regulation of macrophage function in innate intestinal immunity. We examined the susceptibility of Pirb-/- and wild-type (WT) mice to dextran sodium sulfate (DSS)-induced colitis. We assessed proinflammatory cytokine release and MAPK and NFκB activation in Pirb-/- and WT macrophages following E. coli stimulation. Macrophage transfer experiments were performed to define the role of PIR-B in the negative regulation of macrophage function in DSS-induced colitis. We also assessed expression of PIR-B human homologs (ILT-2 and ILT-3) in colon biopsy samples from healthy individuals (controls) and patients with IBD. Pirb-/- mice had increased susceptibility to DSS-induced colitis. In vitro analysis demonstrated increased production of proinflammatory cytokines (IL-6, IL-1β and TNF-α) and activation of MAPK and NFκB in Pirb-/- macrophages following bacterial activation. Adoptive transfer of bone marrow-derived Pirb-/- macrophages into WT mice was sufficient to increase disease susceptibility. ILT-2 and ILT-3 were expressed on CD68+ and CD68- mononuclear cells and intestinal epithelium in colon biopsy samples from patients and controls. PIR-B negatively regulates macrophage functions in response to pathogenic bacteria and chronic intestinal inflammatory responses. Inhibitory receptors such as PIR-B might be used as therapeutic targets for treatment of patients with IBD.
登录
查看更多内容
影响因子：
7.3
作者：
Marks, D. J. B.;Segal, A. W.
通讯作者：
Segal, A. W.
配对的免疫球蛋白样受体PIR-A和PIR-B的生化性质和细胞分布。
影响因子：
15.3
作者：
Kubagawa, H;Chen, C C;Ho, L H;Shimada, T S;Gartland, L;Mashburn, C;Uehara, T;Ravetch, J V;Cooper, M D
通讯作者：
Cooper, M D
影响因子：
3.1
作者：
Cai, J;Jiang, WG;Boulton, M
通讯作者：
Boulton, M
DOI：
10.1152/ajpgi.00453.2007
发表时间：
2008-03-01
影响因子：
4.5
作者：
Ghia, Jean-Eric;Galeazzi, Francesca;Collins, Stephen
通讯作者：
Collins, Stephen
影响因子：
24.5
作者：
MAHIDA, YR;PATEL, S;JEWELL, DP
通讯作者：
JEWELL, DP