Mechanisms of TRAF3 regulation of TLR signaling in B lymphocytes

Abstract Toll-like receptors (TLRs) are pattern recognition that bridge the innate and adaptive immune system critical for host defense. TLR signaling to B cells is important in normal immunity, but also implicated autoimmune disease cell lymphomas (BCL). Most studies focus on role of TLRs myeloid populations. However, express most highly responsive ligands, yet TLR-mediated pathways understudied. Previous from our lab show TRAF3 inhibits functions, including cytokine production, Ig isotype switching, antibody production response ligands 3, 4, 7/8 9. A key knowledge gapis identifying molecular mechanisms by which mediates this regulation. Our working hypothesisis cell-TRAF3 regulates recruitment and/or post-translational modification specific complex proteins. recent data forms a heterocomplex with TRAF6, associating tyrosine kinase Syk. In absence TRAF3, TRAF6 shows greater association several proteins, MyD88, IRAK1 This suggests may inhibit access complex, thus early signaling. addition, work introduces Syk cells. activation enhanced 4 7. Inhibition revealed downstream effects NFκB activation. Further aim at providing new insights into contributing regulation VA Merit Review I01 BX001702 NIH P50 CA97274 RO1 AI5107312000000113259002001 T32 Training Grant AI07485 AI1762656