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- Title
Regulatory B cell is critical in bone union process through suppressing proinflammatory cytokines and stimulating Foxp3 in Treg cells.
- Authors
Sun, Guojing; Wang, Yicun; Ti, Yunfan; Wang, Jun; Zhao, Jianning; Qian, Hongbo
- Abstract
Bone fractures may result in delayed union ( DU) or non-union ( NU) in some patients. Evidence suggests that the skewing of the immune system toward the proinflammatory type is a contributing factor. Because B cells were previously found to infiltrate the fracture healing site at abundant levels, we examined the regulatory B cells (Bregs) in DU/ NU patients. In bone fracture patients with normal healing, the frequency of interleukin ( IL)-10-expressing B cells was significantly upregulated in the early healing process (6 weeks post-surgery) and was downregulated later on (18 weeks post-surgery), whereas in DU/ NU patients, the early upregulation of IL-10-expressing B cells was missing. The majority of IL-10-expressing B cells were concentrated in the IgM+ CD27+ fraction in both controls and patients. IgM+ CD27+ B cells effectively suppressed interferon gamma ( IFN-γ), tumor necrosis factor alpha ( TNF-α), and IL-2 expression from CD4+ T cells, as well as IFN-γ and TNF-α expression from CD8+ T cells. The IgM+ CD27+ B cell-mediated suppression was restricted to the sample from the early healing time point in controls, as the IgM+ CD27+ B cells from normal healing patients later on or from DU/ NU patients did not present significant regulatory function. In addition, culturing of CD4+ CD25+ Tregs with IgM+ CD27+ B cells from controls at early healing time point resulted in higher Foxp3 expression, a function absent in controls at later time point, or in DU/ NU patients. In conclusion, our results support a role of B cell-mediated regulation early during the bone healing process.
- Subjects
BONE cells; PHYSIOLOGICAL effects of cytokines; INTERLEUKIN-10 receptors; INTERFERON gamma; TUMOR necrosis factors; PHYSIOLOGY; TUMOR treatment
- Publication
Clinical & Experimental Pharmacology & Physiology, 2017, Vol 44, Issue 4, p455
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12719