| First Author | Pore D | Year | 2016 |
| Journal | J Immunol | Volume | 196 |
| Issue | 2 | Pages | 558-62 |
| PubMed ID | 26673134 | Mgi Jnum | J:251328 |
| Mgi Id | MGI:6101663 | Doi | 10.4049/jimmunol.1502098 |
| Citation | Pore D, et al. (2016) Cutting Edge: Ezrin Regulates Inflammation by Limiting B Cell IL-10 Production. J Immunol 196(2):558-62 |
| abstractText | IL-10 produced by B cells is important for controlling inflammation, thus underscoring the need to identify mechanisms regulating its production. In this study, we demonstrate that conditional deletion of ezrin in B cells increases IL-10 production induced by TLR4 ligation. The MyD88-independent Toll/IL-1R domain-containing adapter inducing IFN-beta-IFN regulatory factor 3 pathway is required for Ezrin-deficient B cells to produce higher IL-10 upon LPS stimulation. Treatment of B cells with a novel small-molecule inhibitor of ezrin induces its dephosphorylation and increases LPS-induced NF-kappaB and IFN regulatory factor 3 activation and IL-10 secretion, indicating a role for threonine 567 phosphorylation of ezrin in limiting IL-10. Loss of ezrin in B cells results in dampened proinflammatory response to a sublethal dose of LPS in vivo, which is dependent on increased IL-10 production. Taken together, our data yield new insights into molecular and membrane-cytoskeletal regulation of B cell IL-10 production and reveal ezrin as a potential therapeutic target in inflammatory diseases. |
