An essential role for IL-17 in preventing pathogen-initiated bone destruction: Recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent signals
An essential role for IL-17 in preventing pathogen-initiated bone destruction: Recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent signals
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DOI：
10.1182/blood-2005-09-010116
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发表时间：
2007-05-01
期刊：
影响因子：
20.3
通讯作者：
Gaffen, Sarah L.
中科院分区：
文献类型：
--
作者：
Yu, Jeffrey J.;Ruddy, Matthew J.;Gaffen, Sarah L.
IL-17及其受体是一个新的炎性细胞因子家族的创始成员。IL-17在类风湿关节炎(RA)相关的骨破坏中起致病作用。然而，IL-17也是通过粒细胞生成和中性粒细胞运输而调节宿主防御的重要因子。因此，IL-17在病原体引发的骨丢失中的作用并不明显。感染引起的骨破坏最常见的形式是牙周病(PD)。帕金森病除了导致严重的发病率外，还是动脉粥样硬化性心脏病和慢性阻塞性肺疾病(COPD)的危险因素。与类风湿性关节炎类似，帕金森病患者的骨质破坏是由免疫反应引起的。然而，中性粒细胞对牙周组织提供了关键的抗菌防御。由于IL-17在RA中具有破坏骨的作用，但却是中性粒细胞的关键调节因子，因此我们研究了IL-17在口腔病原体牙龈卟啉单胞菌引起的炎症性骨丢失中的作用。这些小鼠表现出增强的牙周骨破坏，这表明IL-17具有骨保护作用，这让人想起中性粒细胞缺乏。尽管IL-17RA缺陷的中性粒细胞在体外功能正常，但IL-17RA基因敲除(IL-17RA(KO))小鼠表现出血清趋化因子水平降低，并伴随着中性粒细胞向骨的迁移减少。一直以来，CXCR2(KO)小鼠对牙槽骨丢失高度敏感；有趣的是，这些小鼠还暗示了趋化因子在维持正常骨稳态中的作用。这些结果表明，IL-17通过中性粒细胞动员在介导宿主防御中发挥了非多余的作用。(C)2007年由美国血液病学会公布。
IL-17 and its receptor are founding members of a novel family of inflammatory cytokines. IL-17 plays a pathogenic role in rheumatoid arthritis (RA)-associated bone destruction. However, IL-17 is also an important regulator of host defense through granulopoiesis and neutrophil trafficking. Therefore, the role of IL-17 in pathogen-initiated bone loss was not obvious. The most common form of infection-induced bone destruction occurs in periodontal disease (PD). In addition to causing significant morbidity, PD is a risk factor for atherosclerotic heart disease and chronic obstructive pulmonary disease (COPD). Similar to RA, bone destruction in PD is caused by the immune response. However, neutrophils provide critical antimicrobial defense against periodontal organisms. Since IL-17 is bone destructive in RA but a key regulator of neutrophils, we examined its role in inflammatory bone loss induced by the oral pathogen Porphyromonas gingivalis in IL-17RA-deficient mice. These mice showed enhanced periodontal bone destruction, suggesting a bone-protective role for IL-17, reminiscent of a neutrophil deficiency. Although IL-17RA-deficient neutrophils functioned normally ex vivo, IL-17RA knock-out (IL-17RA(KO)) mice exhibited reduced serum chemokine levels and concomitantly reduced neutrophil migration to bone. Consistently, CXCR2(KO) mice were highly susceptible to alveolar bone loss; interestingly, these mice also suggested a role for chemokines in maintaining normal bone homeostasis. These results indicate a nonredundant role for IL-17 in mediating host defense via neutrophil mobilization. (C) 2007 by The American Society of Hematology.