BCAP negatively regulates TLR signaling in macrophages (116.13)

• DOI: 10.4049/jimmunol.186.supp.116.13
• Publication Date: 2023-01-01T05:15:15Z
• Authors: Minjian Ni; Alexander MacFarlane; Kerry Campbell; Clifford Lowell; Jessica Hamerman
• Keywords: Wortmannin; Phosphoinositide 3-kinase; Proinflammatory cytokine

Abstract B cell adaptor for phosphoinositide 3-kinase (BCAP) was originally identified as an molecule that binds to the p85 subunit of phosphatidylinositol (PI3K). BCAP-deficient mice have decreased numbers mature cells and attenuated function due defects in receptor signaling. BCAP is also expressed macrophages activates PI3K downstream Toll-like (TLR) ligation. Here we investigated responses stimulation through TLRs. produced higher concentrations inflammatory cytokines response a variety pathogenic stimuli vitro. Additionally, more IL-12 LPS vivo. The TLR mediated Akt activation impaired macrophages. Furthermore, inhibitor wortmannin enhanced proinflammatory cytokine production wild type but not In cells, YXXM motifs are required BCR induced activation. Surprisingly, found only partially responsible negative regulation signaling constitutively phosphorylated associated with resting macrophages, and, unlike does require Syk its phosphorylation. Taken together, our findings show negatively regulates partly TLR-mediated