Interleukin-35 -producing B Cells Rescues Inflammatory Bowel Disease in a Mouse Model Via STAT3 Phosphorylation and Intestinal Microbiota Modification

Interleukin-35 (IL-35)-producing B cells (IL-35B cells) play an important role in diseases, and the expansion of IL-35 immune cells have been observed in inflammatory bowel disease (IBD). However, how IL-35B cells function and the manner in which they perform their roles remain unclear. In this study, human samples and animal models were used to confirm the expansion of IL-35B cells during IBD. In addition, by using il12a and ebi3 mice, we demonstrated that the regulatory role of B cells in IBD depends on IL-35. Mechanically, IL-35B cells can promote its own expansion through endocrine actions and depend on the transcription factor signal transducer and activator of transcription 3. Interestingly, we found that the diversity of intestinal microbes and expression of microbial metabolites decreased during IBD. IL-35B cells promote the high expression of indoleacetic acid (IAA), and exogenous metabolite supplementation with IAA can further promote the expansion of IL-35B cells and rescues the disease. This study provides a new concept for the regulatory model of B cells and a new approach for the treatment of IBD.