Drug design, development and therapy · 2026
Apigenin Upregulates Regulatory B Cells, Suppresses Class Switch Recombination, and Restores Immune Homeostasis to Treat Autoimmune Arthritis and Sepsis.
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Chen Hong, Huang Yilian, He Yufu, Zha Menglei, Liu Xin, Lin Tianqiong, Li Lei, He Ziyi, Zheng Song Guo, Shao Yiming, Luo Aoxiang, Sun Jianbo
Аннотация
BACKGROUND: Restoring immune homeostasis is crucial for inflammation resolution, in which B cells play dual regulatory roles. A promising therapeutic strategy involves simultaneously suppressing proinflammatory B-cell activity while enhancing regulatory B cells (Bregs). Natural anti-inflammatory compounds, such as the flavonoid apigenin (API), may achieve this dual immunomodulation, yet the precise mechanisms of API on B cells remain incompletely understood.
PURPOSE: This study aimed to elucidate how API modulates B cells to exert immunoregulatory and protective effects in inflammatory conditions.
DESIGN: In vitro B-cell functional and molecular assays were integrated with two mechanistically distinct in vivo models-collagen-induced arthritis (CIA) in DBA/1 mice and cecal ligation and puncture (CLP)-induced sepsis in C57BL/6 mice-to evaluate API's dual immunomodulatory effects and therapeutic potential.
METHODS: B cells from mouse splenocytes (n=5 per group) or human PBMCs (n=5 healthy donors) were assessed for differentiation, cytokine production, class switch recombination (CSR), and signaling pathways. p38 MAPK involvement was examined using pathway-specific inhibitors. In vivo, disease severity, survival, immune phenotypes, cytokines, and histopathology were evaluated.
RESULTS: API increased IL-10⁺ Breg frequency by ~2-fold (P < 0.001) and reduced Aicda expression by ~60% (P < 0.001), while suppressing plasma cell differentiation via Prdm1 downregulation. These effects were p38 MAPK-dependent. In CIA mice, API reduced arthritis scores by ~45% (P < 0.01); in CLP-induced sepsis, 7-day survival improved from 0% to 70% (P < 0.05), with attenuated lung injury and pro-inflammatory cytokine levels. Collectively, API promotes immune homeostasis restoration in both chronic autoimmune and acute inflammatory settings.
CONCLUSION: API restores immune homeostasis in both chronic autoimmune and acute inflammatory settings by coordinating Breg differentiation and suppressing pathogenic B-cell responses, highlighting B-cell-centric immune rebalancing as a promising therapeutic strategy for inflammatory diseases.
PURPOSE: This study aimed to elucidate how API modulates B cells to exert immunoregulatory and protective effects in inflammatory conditions.
DESIGN: In vitro B-cell functional and molecular assays were integrated with two mechanistically distinct in vivo models-collagen-induced arthritis (CIA) in DBA/1 mice and cecal ligation and puncture (CLP)-induced sepsis in C57BL/6 mice-to evaluate API's dual immunomodulatory effects and therapeutic potential.
METHODS: B cells from mouse splenocytes (n=5 per group) or human PBMCs (n=5 healthy donors) were assessed for differentiation, cytokine production, class switch recombination (CSR), and signaling pathways. p38 MAPK involvement was examined using pathway-specific inhibitors. In vivo, disease severity, survival, immune phenotypes, cytokines, and histopathology were evaluated.
RESULTS: API increased IL-10⁺ Breg frequency by ~2-fold (P < 0.001) and reduced Aicda expression by ~60% (P < 0.001), while suppressing plasma cell differentiation via Prdm1 downregulation. These effects were p38 MAPK-dependent. In CIA mice, API reduced arthritis scores by ~45% (P < 0.01); in CLP-induced sepsis, 7-day survival improved from 0% to 70% (P < 0.05), with attenuated lung injury and pro-inflammatory cytokine levels. Collectively, API promotes immune homeostasis restoration in both chronic autoimmune and acute inflammatory settings.
CONCLUSION: API restores immune homeostasis in both chronic autoimmune and acute inflammatory settings by coordinating Breg differentiation and suppressing pathogenic B-cell responses, highlighting B-cell-centric immune rebalancing as a promising therapeutic strategy for inflammatory diseases.