Circulating T helper 9 cells and increased serum interleukin‐9 levels in patients with knee osteoarthritis

Abstract

The purpose of this study was to examine the roles of T helper 9 (Th9) cells and the serum interleukin (IL)-9 level in the pathogenesis of osteoarthritis (OA). The numbers of IL-9(+) CD4(+) CD8(-) T cells, interferon (IFN)-γ+ CD4(+) CD8(-) T cells, IL-4(+) CD4(+) CD8(-) T cells, and IL-17A(+) CD4(+) CD8(-) T cells in 25 OA patients and 13 healthy controls (HC) were examined by flow cytometry. The serum concentrations of IL-9, IL-4, IL-17A, and IFN-γ were also determined. The numbers of CD4(+) CD45RO(+) T cells, Th9 cells, Th1 cells, and Th17 cells in OA patients were significantly higher than those in HCs. Furthermore, serum IL-9, IL-17A, and IFN-γ levels in OA patients were higher than those in HCs. The number of Th9 cells was positively correlated with the number of Th17 cells in OA patients. Furthermore, greater numbers of Th9 cells were positively associated with elevated C-reactive protein, and both Th9 cells and IL-9 levels were positively correlated with the Western Ontario and McMaster Universities Osteoarthritis index in OA patients. Th9 cell numbers and IL-9 levels are correlated with OA patient symptoms and joint functionality and may be a marker of disease activity.

T Cells in Osteoarthritis: Alterations and Beyond

“…In patients with OA, the majority of CD4 + T cells in the synovial fluid and synovial tissue are CD45RO + and CD45RA − , suggesting that an accumulation of CD45RO + memory CD4 + T cells is a generalized phenomenon in OA joints (88). Similarly, a study with 25 OA patients and 13 healthy controls revealed that the number of circulating CD4 + CD45RO + T cells was significantly higher in patients with OA than in healthy controls (47). Other evidence for the possible involvement of Tm cells in the pathogenesis of OA includes the detection of the regulated on activation, normal T cell expressed, and secreted chemokine (a potent chemoattractant for leukocytes, such as CD45RO + memory T cells) and CD29 (a 1 integrin expressed by Tm cells) in the synovial fluid of OA patients (35, 37, 89).…”

“…Similarly, no variation in either the percentage or the absolute number of circulating Th1 cells (CD4 + IFN-γ + T cells) has been found between patients with OA and healthy controls (46). However, in a study with 25 OA patients and 13 healthy controls, the number of circulating Th1 cells (IFN-γ + CD4 + CD8 − T cells) and the level of serum IFN-γ were found to be significantly higher in patients with OA than in healthy controls (47). The difference in the markers (CD4 + IFN-γ + vs. IFN-γ + CD4 + CD8 − ) used in the two studies to define Th1 cells may account for this discrepancy.…”

“…For example, a high level of IL-9 has been detected in the peripheral blood and synovial fluid of OA patients, and the activation of purified CD3 + cells from the peripheral blood and synovial fluid of patients with OA produces a high level of IL-9, although lower than that observed in RA or PsA patients (58). Even more importantly, in a study with 25 OA patients and 13 healthy controls, the number of circulating Th9 cells and serum IL-9 level were found to be significantly higher in OA patients than in healthy controls (47). This study also found that the number of circulating Th9 cells was positively associated with the level of C-reactive protein in OA patients and that both the number of Th9 cells and the level of serum IL-9 were positively correlated with OA index (47).…”

“…Even more importantly, in a study with 25 OA patients and 13 healthy controls, the number of circulating Th9 cells and serum IL-9 level were found to be significantly higher in OA patients than in healthy controls (47). This study also found that the number of circulating Th9 cells was positively associated with the level of C-reactive protein in OA patients and that both the number of Th9 cells and the level of serum IL-9 were positively correlated with OA index (47). …”

“…In a rat model of OA induced by the injection of papain and l -cysteine into the right knee joint, the OA rats were found to have a higher serum IL-17 level than the control rats (68). In addition, in a study with 25 OA patients and 13 healthy controls, the number of circulating Th17 cells and the level of serum IL-17 were found to be significantly higher in patients with OA than in healthy controls (47). As in the case of Th1 cells, variation in the markers used to define Th17 cells (CD4 + IL-17 + vs. IL-17 + CD4 + CD8 − ) and the patients selected for investigation (e.g., diagnosis standard, disease index, patients’ background) may account for this discrepancy.…”