| First Author | Oka A | Year | 2019 |
| Journal | Cells | Volume | 8 |
| Issue | 10 | PubMed ID | 31546615 |
| Mgi Jnum | J:293658 | Mgi Id | MGI:6453284 |
| Doi | 10.3390/cells8101121 | Citation | Oka A, et al. (2019) Phosphoinositide 3-Kinase P110delta-Signaling Is Critical for Microbiota-Activated IL-10 Production by B Cells that Regulate Intestinal Inflammation. Cells 8(10):1121 |
| abstractText | The phosphoinositide 3-kinase catalytic subunit p110delta (PI3Kdelta) gene maps to a human inflammatory bowel diseases (IBD) susceptibility locus, and genetic deletion of PI3Kdelta signaling causes spontaneous colitis in mice. However, little is known regarding the role of PI3Kdelta on IL-10-producing B cells that help regulate mucosal inflammation in IBD. We investigated the role of PI3Kdelta signaling in B cell production of IL-10, following stimulation by resident bacteria and B cell regulatory function against colitis. In vitro, B cells from PI3Kdelta(D910A/D910A) mice or wild-type B cells treated with PI3K specific inhibitors secreted significantly less IL-10 with greater IL-12p40 following bacterial stimulation. These B cells failed to suppress inflammatory cytokines by co-cultured microbiota-activated macrophages or CD4(+) T cells. In vivo, co-transferred wild-type B cells ameliorated T cell-mediated colitis, while PI3Kdelta(D910A/D910A) B cells did not confer protection from mucosal inflammation. These results indicate that PI3Kdelta-signaling mediates regulatory B cell immune differentiation when stimulated with resident microbiota or their components, and is critical for induction and regulatory function of IL-10-producing B cells in intestinal homeostasis and inflammation. |
