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首页 » Science报道 » Sci Transl Med:IL-17细胞因子在LAD-相关性牙骨质流失中起着关键性的作用

Sci Transl Med:IL-17细胞因子在LAD-相关性牙骨质流失中起着关键性的作用

来源:EurekAlert! 2014-03-27 23:10

据一项新的研究提示,因为牙龈疾病而导致的慢性炎症和骨质流失可通过针对细胞因子IL-17的抗体的治疗而被逆转。患有一种叫做白细胞粘附缺陷I型(LAD-I)的罕见疾病的患者会遭受频繁且反复的感染,其中包括那些早在婴儿期就开始的感染,尤其是牙周炎(或牙龈疾病)。

即使得到治疗,患者仍然会失去全部或大多数的牙齿。目前,对这些患者还没有有效的治疗选择。在LAD-I中所见的骨质流失被认为是由于缺乏嗜中性粒细胞而引起的;嗜中性粒细胞是免疫细胞,它们在正常情况下会因应感染或炎症而快速地向牙龈组织移动。Niki Moutsopoulos、George Hajishengallis 及其同事在LAD-I患者中看到嗜中性粒细胞数的减少及严重的牙龈炎症。

他们还注意到,这些病人有着高浓度的IL-17——这是一种因为嗜中性粒细胞的阙如而调节出现异常的细胞因子,且它们常常出现在像牙齿和牙龈等位置,而这些位置存在着大量的细菌。研究人员在转向小鼠研究时发现,当中性粒细胞在牙龈组织中阙如时,IL-17也会过度产生并会驱使过度的炎症及细菌的积聚。对小鼠用该细胞因子抗体进行治疗可降低细菌载量及减少炎症和骨质流失。

这些结果提示,在疾病早期给予患者抗体可预防牙骨质的流失。 (生物谷Bioon.com)

生物谷推荐的英文摘要:

Sci Transl Med  doi:10.1126/scitranslmed.3007696

Defective Neutrophil Recruitment in Leukocyte Adhesion Deficiency Type I Disease Causes Local IL-17–Driven Inflammatory Bone Loss

Niki M. Moutsopoulos1,*, Joanne Konkel2, Mojgan Sarmadi1, Mehmet A. Eskan3, Teresa Wild1, Nicolas Dutzan1, Loreto Abusleme1, Camille Zenobia4, Kavita B. Hosur4, Toshiharu Abe4, Gulbu Uzel5, WanJun Chen2, Triantafyllos Chavakis6, Steven M. Holland5 and George Hajishengallis4,*

Leukocyte adhesion deficiency type I (LAD-I), a disease syndrome associated with frequent microbial infections, is caused by mutations on the CD18 subunit of β2 integrins. LAD-I is invariably associated with severe periodontal bone loss, which historically has been attributed to the lack of neutrophil surveillance of the periodontal infection. We provide an alternative mechanism by showing that the cytokine interleukin-17 (IL-17) plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients or in LFA-1 (CD11a/CD18)–deficient mice—which exhibit the LAD-I periodontal phenotype—was associated with excessive production of predominantly T cell–derived IL-17 in the periodontal tissue, although innate lymphoid cells also contributed to pathological IL-17 elevation in the LFA-1–deficient mice. Local treatment with antibodies to IL-17 or IL-23 in LFA-1–deficient mice not only blocked inflammatory periodontal bone loss but also caused a reduction in the total bacterial burden, suggesting that the IL-17–driven pathogenesis of LAD-I periodontitis leads to dysbiosis. Therefore, our findings support an IL-17–targeted therapy for periodontitis in LAD-I patients.

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