2025年江伯倫老師實驗室論文發表--免疫所碩士班黃羿苹
B Cells Induced Regulatory T Cells Attenuated the Classical M1 Polarization of Mouse Bone Marrow-Derived Macrophages
Yi-Ping Huang1, Chien-Hui Chien2, Li-Chieh Wang3, Bor-Luen Chiang1,3,4
- Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu County, Taiwan.
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
- Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan
Abstract
Regulatory T (Treg) cells are effective immunomodulators of adaptive and innate immune responses. Our previous studies have demonstrated that B-cell-induced CD4+Foxp3− regulatory T cells, referred to as Treg-of-B cells, exert suppressive capacity, inhibiting CD4+CD25- T-cell proliferation and inflammasome activation. In the present study, Treg-of-B cells downregulated proinflammatory M1-like markers and partially induced M2-like genes in unpolarized bone marrow-derived macrophages (BMDMs), as evidenced by RNA expression of Nos2, Arg1, Retnla, Mrc1, and Egr2. Treg-of-B cells decreased the RNA levels of Nos2, Tnfa, Cd86, and Cxcl9, and the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and nitrite in LPS/interferon (IFN)-γ-stimulated M1-like macrophages in a dose-dependent manner. These cells also secreted Th2 cytokines, including IL-10, IL-4, and IL-13, with enhanced cytokine production observed upon cocultured with macrophages. Mechanistically, Treg-of-B cells exerted their modulatory effect via both cell-cell contact and contact-dependent induction of soluble mediators, particularly Th2 cytokines. Furthermore, Treg-of-B cells promoted IκBα accumulation and suppressed RNA expression of Kruppel-like factor 4 (Klf4), thereby inhibiting NF-κB activation. These findings suggest that Treg-of-B cells regulate macrophage plasticity and might prevent excessive inflammation.
Keywords: Treg-of-B cells, macrophages, IL-10, IL-4, nitrite, KLF4
Sci Rep 2025 October, 15(1): 35537
doi: 10.1038/s41598-025-19445-1