| First Author | Schmidt NW | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 10 | Pages | 7203-10 |
| PubMed ID | 17082638 | Mgi Jnum | J:140621 |
| Mgi Id | MGI:3814168 | Doi | 10.4049/jimmunol.177.10.7203 |
| Citation | Schmidt NW, et al. (2006) Bruton's tyrosine kinase is required for TLR-induced IL-10 production. J Immunol 177(10):7203-10 |
| abstractText | Bruton's tyrosine kinase (Btk) is a critical signaling mediator downstream of the B cell Ag receptor. X-linked agammaglobulinemia is caused by mutations in Btk resulting in multiple defects in B cell development and function, and recurrent bacterial infections. Recent evidence has also supported a role for Btk in TLR signaling. We demonstrate that Btk is activated by TLR4 in primary macrophages and is required for normal TLR-induced IL-10 production in multiple macrophage populations. Btk-deficient bone marrow-derived macrophages secrete decreased levels of IL-10 in response to multiple TLR ligands, compared with wild-type (WT) cells. Similarly, Btk-deficient peritoneal and splenic macrophages secrete decreased IL-10 levels compared with WT cultures. This phenotype correlates with Btk-dependent induction of NF-kappaB and AP-1 DNA binding activity, and altered commensal bacteria populations. Decreased IL-10 production may be responsible for increased IL-6 because blocking IL-10 in WT cultures increased IL-6 production, and supplementation of IL-10 to Btk-deficient cultures decreased IL-6 production. Similarly, injection of IL-10 in vivo with LPS decreases the elevated IL-6 serum levels during endotoxemia in Btk-deficient mice. These data further support a role for Btk in regulating TLR-induced cytokine production from APCs and provide downstream targets for analysis of Btk function. |
