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

Abstract

Retrospective single-center study. 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). NBF in AS is unknown. Since there are balances of bone remodeling in human body and proinflammatory helper T cells TH17 promoted bone resorption. 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. 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). 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. N/A.