Increased frequency of peripheral blood follicular helper T cells and elevated serum IL-21 levels in patients with knee osteoarthritis

Abstract

An aberrant immune response has been implicated in the pathogenesis of osteoarthritis (OA). However, the role of peripheral blood follicular helper T (TFH) cells in the pathogenesis of OA has yet to be elucidated. The purpose of the present study was to examine the role of TFH cells and serum interleukin-21 (IL-21) in the pathogenesis of OA. Frequency of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and IL-21+ CXCR5+CD4+ T cells in 40 patients with OA and 13 healthy controls (HCs) were examined by flow cytometry. The disease state in individual patients was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Concentrations of serum IL-21, interferon-γ (INF-γ), IL-4, IL-17A, and C-reactive protein (CRP) were determined, and the erythrocyte sedimentation rate (ESR) was measured. The percentages of CXCR5+CD4+ cells, PD-1+CXCR5+CD4+, ICOS+CXCR5+CD4+ and IL-21+CXCR5+CD4+ T cells in OA patients were significantly higher than those in the HCs. Furthermore, serum IL-21, IL-17A and IFN-γ levels in OA patients were significantly higher than those in HCs. Expression of IL-21+TFH cells in OA patients demonstrated a positive correlation with OA disease activity, CRP levels and WOMAC. TFH cells and IL-21 appear to serve an important role in the progression of OA. IL-21+TFH cells may prove to be a marker of OA disease activity.

The Role of Inflammation in the Pathogenesis of Osteoarthritis

“…Increased infiltration of leukocytes (macrophages, T-lymphocytes, Blymphocytes, and neutrophils) in the synovium, particularly within the subintimal layer, is a characteristic of osteoarthritis [14]. Shan et al reported elevated PD1+CXCR5+ CD4+ T cells, ICOS+CXCR5+CD4+ T cells, and IL 21+ CXCR5+CD4+ T cells in peripheral blood of patients with osteoarthritis [15]. CD4+ T cell is the T helper cell (Th cell) which may induce inflammation in the early stage of osteoarthritis.…”

“…CD4+ T cell is the T helper cell (Th cell) which may induce inflammation in the early stage of osteoarthritis. C-X-C chemokine receptor type 5 (CXCR5), inducible costimulator (ICOS), and programmed cell death 1 (PD-1) are known to be expressed by the Th cell [15].…”

“…Some of the cytokines shown to increase in osteoarthritis are IL-18, TGFβ1 [14], IL-1 receptor (IL-1R) [59], and IL-1 alpha (IL-1α) [23]. Shan et al showed enhanced serum IL-21, IL-17A, and IFN-γ levels in patients with osteoarthritis compared to controls [15]. IL-21 also upregulates RANKL expression, thereby stimulating bone marrow stem cells to differentiate into mature osteoclasts [60].…”

T Cells in Osteoarthritis: Alterations and Beyond

“…In the latter study, the frequency of ICOS + , PD-1 + , and IL-21 + CXCR5 + CD4 + T cells in the peripheral blood of 40 patients with OA and 13 healthy controls was examined by flow cytometry, and the concentration of serum IL–21 was also determined. Compared with the healthy controls, the OA patients showed higher percentages of CXCR5 + CD4 + , PD-1 + CXCR5 + CD4 + , ICOS + CXCR5 + CD4 + , and IL-21 + CXCR5 + CD4 + T cells (83). Shan et al (83) also found that OA patients exhibited higher levels of serum IL-21 than healthy controls and, even more importantly, that the expression of IL-21 + Tfh cells in OA patients was positively correlated with the disease activity of OA (83).…”

“…Compared with the healthy controls, the OA patients showed higher percentages of CXCR5 + CD4 + , PD-1 + CXCR5 + CD4 + , ICOS + CXCR5 + CD4 + , and IL-21 + CXCR5 + CD4 + T cells (83). Shan et al (83) also found that OA patients exhibited higher levels of serum IL-21 than healthy controls and, even more importantly, that the expression of IL-21 + Tfh cells in OA patients was positively correlated with the disease activity of OA (83). The latter study suggests that Tfh cells play a critical role in the pathogenesis and progression of OA.…”