Differential regulation of TLR4 expression in human B cells and monocytes.
Toll-like receptor 4 (TLR4) is an innate immune receptor that is constitutively and inducibly activated in monocytes. Although TLR4 is expressed at very low levels on human B cells from healthy individuals, recent reports showed that TLR4 expression and function is elevated in B cells from inflammatory disease patients. New data showed that TLR4 expression on B cells is increased upon stimulation through surface Igμ and CD40 in combination with IL-4. In contrast, monocyte stimulation through CD40 and IL-4 receptors decreased TLR4 surface expression. Analysis of molecular signatures of TLR4 activation in stimulated B cells suggested that TLR4 is regulated by different mechanisms in B cells compared to monocytes. PU.1 and interferon regulatory factor association with the TLR4 promoter are sufficient for TLR4 transcription, but are not sufficient for surface TLR4 expression on B cells. In contrast, the PU.1/IRF combination is sufficient for surface TLR4 expression on monocytes. These data identify mechanisms that can activate B cell TLR4 expression in inflammatory disease patients, and demonstrate that B cells have additional layers of TLR4 regulation absent in monocytes.
Department of Medicine, Section of Infectious Diseases, Evans Biomedical Research Center, Boston Medical Center, Boston, MA 02118, USA.
Lisa M
LM
Ganley-Leal
YanMei
Y
Liang
Madhumita
M
Jagannathan-Bogdan
Francis A
FA
Farraye
Barbara S
BS
Nikolajczyk
D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003424:Crohn Disease / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4