IKKβ increases neuropilin-2 and promotes the inhibitory function of CD9+ Bregs to control allergic diseases

作者：Wang, Yiyuan; Deng, Wende; Liu, Juan; Yang, Qin; Chen, Ziye; Su, Jianbing; Xu, Jialan; Liang, Qinghe; Li, Ting; Liu, Liang^*; Li, Xiaojuan^*

来源：Pharmacological Research, 2022, 185: 106517.

DOI：10.1016/j.phrs.2022.106517

• Regulatory B cells
• IKK beta
• CD9
• Nrp2
• IL-10

Regulatory B cells (Bregs) potently suppress immune disorders, including allergic contact hypersensitivity (CHS). IKK beta overactivation is prominent in various inflammatory diseases. However, its effect on Bregs has not been defined. This study is to investigate the new regulator and inhibitory mechanism of Bregs. Ikk beta(C46A) transgenic mice with a Cys46 mutation, resulting in increased IKK beta activation, were employed for analysis. IL-10-competent CD9(+) Bregs were expanded in Ikk beta(C46A) mice and B cell specific-Ikk beta(C46A) mutation mice. Ikk beta(C46A) mutant CD9(+) Bregs had stronger suppressive effects on CD4(+) and CD8(+) T cells in vitro and CHS responses in vivo. The inhibitory CD9(+) Bregs from IIkk beta(C46A) mice were characterized by upregulated Neumpilin 2 (Nrp2) and IL-10 in comparison with that of Ikk beta(wt) mice. Interestingly, increased expression of Nrp2 was observed in CD9(+) Bregs compared with that of CD9(-) B cells in wild-type mice. The suppressive activity of wild-type CD9(+) Bregs in vitro was attenuated by inhibition of Nrp2 on Bregs or silencing its ligand Sema3f on CD4(+) T cells. Our findings delineate a distinct role of IKK beta activation in enhancing Bregs to disturb the immune balance. It identifies Nrp2 as a novel regulatory molecule of Bregs that partly contributes to B cell-mediated immune tolerance.

• 单位
  i; 南方医科大学; 广州中医药大学