Treg 通过分泌白细胞介素-10 抑制 TH17 促进强直性脊柱炎新骨形成。
Treg-promoted New Bone Formation Through Suppressing TH17 by Secreting Interleukin-10 in Ankylosing Spondylitis.
机构信息
Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi, China.
Department of Orthopedics, Han Zhong Central Hospital, Hanzhong, Shanxi, China.
出版信息
Spine (Phila Pa 1976). 2019 Dec 1;44(23):E1349-E1355. doi: 10.1097/BRS.0000000000003169.
STUDY DESIGN
Retrospective single-center study.
OBJECTIVE
We want to know whether interleukin (IL)-10-secreting regulatory T cells (Treg) promote the new bone formation (NBF) through suppressing TH17 in ankylosing spondylitis (AS).
SUMMARY OF BACKGROUND DATA
NBF in AS is unknown. Since there are balances of bone remodeling in human body and proinflammatory helper T cells TH17 promoted bone resorption.
METHODS
Eighteen AS patients with or without NBF (both nine cases) and nine healthy individuals were selected and the demographic data, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), MRI sacroiliitis score (MRISIS), and computer tomography sacroiliitis score (CTSIS) were recorded. Removed hip ligament tissue in the lesions after arthroplasty was collected and the lymphocytes and the peripheral blood mononuclear cells were prepared. Second, pathological section in hematoxylin-eosin stain were analyzed and flow cytometry and quantitative polymerase chain reaction analyses were carried out to detect the levels of TH17, Treg, IL-10, and nuclear factor (NF)-κB, and the relevance between them. The effect of Treg on TH17 was further analyzed by using Transwell coculturing.
RESULTS
Compared to AS patients without NBF, AS patients with NBF had significantly higher CTSIS and complications (P < 0.05 and 0.01, respectively), but significantly lower BASDAI (3.0 ± 0.4) and MRISIS (3.3 ± 0.8) (P < 0.01 and 0.05, respectively) and no acute inflammation in HE stain for hip joint. Compared to healthy donors, the ratio of TH17/Treg was significantly higher in AS patients without NBF and lower in AS patient with NBF (both P < 0.01) in flow cytometry analysis (FCA). Furthermore, TH17 significantly decreased after indirectly coculturing with Treg in FCA (P < 0.01). Finally, IL-10 had significantly higher mRNA expression in AS patients with NBF (P < 0.01), and NF-κB had significantly higher mRNA expression in AS patients without NBF (P < 0.05) than healthy donors. Only the mRNA expression of IL-10 was significantly correlated to the ratio of TH17/Treg (r = -0.93, P < 0.01).
CONCLUSION
Treg-induced NBF of AS through suppressing TH17 by secreting IL10 and declining of the ratio of TH17/Treg indicated the development of NBF. This is important not only for screening development of NBF, but also for control of NBF of AS by immune therapy.
LEVEL OF EVIDENCE
N/A.
研究设计
回顾性单中心研究。
目的
我们想知道白细胞介素（IL）-10 分泌的调节性 T 细胞（Treg）是否通过抑制强直性脊柱炎（AS）中的 TH17 来促进新骨形成（NBF）。
背景资料概要
AS 中的 NBF 尚不清楚。由于人体骨骼重塑存在平衡，辅助性 T 细胞 TH17 促进了骨吸收。
方法
选择了 18 例伴有（9 例）或不伴有 NBF（均为 9 例）的 AS 患者和 9 例健康个体，记录了人口统计学数据、巴斯强直性脊柱炎疾病活动指数（BASDAI）、磁共振成像骶髂关节炎评分（MRISIS）和计算机断层扫描骶髂关节炎评分（CTSIS）。在关节置换术后病变处切除髋关节韧带组织，制备淋巴细胞和外周血单核细胞。然后，进行苏木精-伊红染色的病理切片分析，并进行流式细胞术和实时定量聚合酶链反应分析，以检测 TH17、Treg、IL-10 和核因子（NF）-κB 的水平，并分析它们之间的相关性。通过 Transwell 共培养进一步分析 Treg 对 TH17 的影响。
结果
与无 NBF 的 AS 患者相比，有 NBF 的 AS 患者的 CTSIS 和并发症明显更高（P<0.05 和 0.01），但 BASDAI（3.0±0.4）和 MRISIS（3.3±0.8）明显更低（P<0.01 和 0.05），髋关节的 HE 染色无急性炎症。与健康供体相比，无 NBF 的 AS 患者的 TH17/Treg 比值在流式细胞术分析（FCA）中明显更高，而有 NBF 的 AS 患者的比值明显更低（均 P<0.01）。此外，在 FCA 中，TH17 经间接与 Treg 共培养后明显减少（P<0.01）。最后，NBF 患者的 IL-10 mRNA 表达明显高于健康供体（P<0.01），而无 NBF 的 AS 患者的 NF-κB mRNA 表达明显高于健康供体（P<0.05）。仅 IL-10 的 mRNA 表达与 TH17/Treg 比值显著相关（r=-0.93，P<0.01）。
结论
Treg 通过分泌 IL10 抑制 TH17 从而诱导 AS 的 NBF，TH17/Treg 比值的下降表明 NBF 的发生。这不仅对筛选 NBF 的发展很重要，而且对通过免疫治疗控制 AS 的 NBF 也很重要。
证据水平
N/A。
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