白细胞介素-9 和白细胞介素-17 的表达差异与巨细胞动脉炎血管壁损伤的不同组织学模式相关。
Difference in the expression of IL-9 and IL-17 correlates with different histological pattern of vascular wall injury in giant cell arteritis.
机构信息
Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo.
Unità Operativa di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti 'Villa Sofia-Cervello', Palermo.
出版信息
Rheumatology (Oxford). 2015 Sep;54(9):1596-604. doi: 10.1093/rheumatology/kev102. Epub 2015 Apr 9.
OBJECTIVE
GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA.
METHODS
Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed were also enrolled to evaluate the effect of glucocorticoids on IL-9 and IL-17 expression.
RESULTS
IL-17 overexpression was observed mainly in arteries with transmural inflammation and vasa vasorum vasculitis. IL-9 overexpression and Th9 polarization predominated in arteries with transmural inflammation and small-vessel vasculitis. The tissue expression of both IL-9 and IL-17 was correlated with the intensity of the systemic inflammatory response. IL-4, TGF-β and thymic stromal lymphopoietin, which are involved in the differentiation of Th9 cells, were overexpressed in arteries with transmural inflammation and small-vessel vasculitis. IL-9R was also overexpressed in GCA arteries with transmural inflammation and was accompanied by increased expression of IL-8.
CONCLUSION
Herein we provide the first evidence that distinct populations of potentially autoreactive T cells, expressing different cytokines (Th17 vs Th9), characterize patients with particular histological subsets of GCA and may thus contribute to the heterogeneity of tissue lesions observed in these patients.
目的
GCA 是一种大、中血管炎,其特征是血管壁损伤的组织学模式多种多样。本研究旨在从免疫学角度对 GCA 的各种组织学模式进行特征描述。
方法
对 35 例经活检证实的 GCA 患者和 15 例正常对照者进行研究。通过 RT-PCR 和免疫组织化学检测动脉活检标本中 IL-8、IL-9、IL-9R、IL-17、IL-4、TGF-β 和胸腺基质淋巴细胞生成素的表达。采用共聚焦显微镜对 IL-9 产生细胞和 IL-9R 表达细胞的表型进行特征描述。还招募了另外 5 例在进行颞动脉活检时接受了泼尼松治疗的患者,以评估糖皮质激素对 IL-9 和 IL-17 表达的影响。
结果
IL-17 过表达主要见于有穿壁性炎症和血管腔血管炎的动脉。IL-9 过表达和 Th9 极化主要见于有穿壁性炎症和小血管血管炎的动脉。组织中 IL-9 和 IL-17 的表达均与全身炎症反应的强度相关。参与 Th9 细胞分化的 IL-4、TGF-β 和胸腺基质淋巴细胞生成素在有穿壁性炎症和小血管血管炎的动脉中过表达。IL-9R 也在有穿壁性炎症的 GCA 动脉中过表达,并伴有 IL-8 的表达增加。
结论
本研究首次提供证据表明,表达不同细胞因子(Th17 与 Th9)的潜在自身反应性 T 细胞的不同群体,可对具有特定组织学亚群的 GCA 患者进行特征描述,从而可能导致这些患者中观察到的组织损伤异质性。