Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the char...Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4^(+) programmed death 1 (PD-1)^(+)Foxp3^(−) T cells in relation to the B-cell response in patients with RA. Methods:This study included 155 patients with RA and 36 age- and sex-matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4^PD-1^(−)Foxp3^(+) T cells, including their proliferation, activation, cytokine production, and capacity to induce B-cell differentiation. Results:The proportion of CD4^(+)PD-1^(+)Foxp3^(−)T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p < 0.001), and this was positively associated with the B-cell response. Compared with CD4^PD-1 ^(+)Foxp3 ^(+) T cells, CD4^(+)PD-1^(+)Foxp3^(−)T cells from patients with RA exhibited increased expression of Ki67 ([6.52 ± 0.41]% vs. [3.87 ± 0.42]%, p < 0.01) and activation markers, produced higher levels of cytokines, and showed enhanced B-cell differentiation. Furthermore, anti-interleukin-6R antagonists decreased the proportion, activation, and cytokine production of CD4^(+)PD-1^(+)Foxp3^(−)T cells in vitro. The frequency of type 2 CD4^(+)PD-1^(+)Foxp3^(−)T cells was significantly higher in patients with RA than that in HCs ([37.27 ± 1.43]% vs. [29.05 ± 1.30]%, p < 0.05). Conclusions:Peripherally expanded CD4^(+)PD-1^(+)Foxp3^(−)T cells in patients with RA, which induced B-cell hyperactivity, may be inclined toward type 2 helper T cells. Our findings revealed a novel T-cell subset that contributes to B-cell hyperactivity in the pathogenesis of RA.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:82071834,82271839,82302047Doctoral Start-up Foundation of Liaoning Province,Grant/Award Numbers:2023−BS-160Dalian Medical University Interdisciplinary Research Cooperation Project Team Funding,Grant/Award Numbers:JCHZ2023010.
文摘Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4^(+) programmed death 1 (PD-1)^(+)Foxp3^(−) T cells in relation to the B-cell response in patients with RA. Methods:This study included 155 patients with RA and 36 age- and sex-matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4^PD-1^(−)Foxp3^(+) T cells, including their proliferation, activation, cytokine production, and capacity to induce B-cell differentiation. Results:The proportion of CD4^(+)PD-1^(+)Foxp3^(−)T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p < 0.001), and this was positively associated with the B-cell response. Compared with CD4^PD-1 ^(+)Foxp3 ^(+) T cells, CD4^(+)PD-1^(+)Foxp3^(−)T cells from patients with RA exhibited increased expression of Ki67 ([6.52 ± 0.41]% vs. [3.87 ± 0.42]%, p < 0.01) and activation markers, produced higher levels of cytokines, and showed enhanced B-cell differentiation. Furthermore, anti-interleukin-6R antagonists decreased the proportion, activation, and cytokine production of CD4^(+)PD-1^(+)Foxp3^(−)T cells in vitro. The frequency of type 2 CD4^(+)PD-1^(+)Foxp3^(−)T cells was significantly higher in patients with RA than that in HCs ([37.27 ± 1.43]% vs. [29.05 ± 1.30]%, p < 0.05). Conclusions:Peripherally expanded CD4^(+)PD-1^(+)Foxp3^(−)T cells in patients with RA, which induced B-cell hyperactivity, may be inclined toward type 2 helper T cells. Our findings revealed a novel T-cell subset that contributes to B-cell hyperactivity in the pathogenesis of RA.
