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Treg-promoted New Bone Formation Through Suppressing Th17 by Secreting Interleukin-10 in Ankylosing Spondylitis

Xu, Fan MD; Guanghao, Chi MD; Liang, Yan MD; Jun, Wang MD; Wei, Wu MD; Baorong, He MD

doi: 10.1097/BRS.0000000000003169
BASIC SCIENCE
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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

Treg-induced new bone formation (NBF) of ankylosing spondylitis (AS) through suppressing Th17 by secreting interleukin-10 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.

Department of Orthopedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shanxi, China

Department of Orthopedics, Han Zhong Central Hospital, Hanzhong, Shanxi, China.

Address correspondence and reprint requests to He Baorong, MD, Department of Orthopedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shanxi 710000, China; E-mail: hebr888@163.com

Received 14 March, 2019

Revised 20 May, 2019

Accepted 10 June, 2019

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work.

No relevant financial activities outside the submitted work.

FX, GC, and LY contributed equally.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.