Helminth-induced CD9+ B-cell subset alleviates obesity-associated inflammation via IL-10 production
2022
Li, Maining | Wang, Huiquan | Ni, Yangyue | Li, Chen | Xu, Xuejun | Zhang, Hao | Xu, Zhipeng | Hou, Min | Ji, Minjun
It has been shown that helminth infection can protect against obesity and improve insulin sensitivity to a certain extent, based on epidemiological investigations and animal experiments. Meanwhile, helminths induce a network of regulatory immune cells, including regulatory B cells (Bregs). However, the molecule characteristics and function of these Bregs in improving whole-body metabolic homeostasis remains largely unclear. We established a mouse model with chronic Schistosoma japonicum infection, and compared the differences in B10 cells (CD19⁺CD5⁺CD1dʰⁱ) and B10⁻ cells (CD19⁺CD5⁻CD1d⁻) from splenic B cells of infected mice using RNA-seq. A unique Breg population was identified. Furthermore, these Bregs were evaluated for their ability to produce inhibitory cytokines in vitro and suppress obesity when adoptively transferred into mice on a high-fat diet. We found that schistosome infection could expand Breg cell populations in mice. CD9 was demonstrated to be a key surface marker for most murine IL-10⁺ B cells in spleen. CD19⁺CD9⁺ B cells produced more IL-10 than conventional B10 cells. Adoptive transfer of CD9⁺ B cells had the capacity to alleviate obesity-associated inflammation via promoting Tregs, Th2 cells and decreasing Th1, Th17 cells in high-fat diet mice. In conclusion, schistosome infection can induce regulatory CD9⁺ B cell production, which plays a critical role in the regulation of metabolic disorders through IL-10 production.
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