CD45 negatively regulates tumour necrosis factor and interleukin-6 production in dendritic cells.
CD45 is known to regulate signalling through many different surface receptors in diverse haemopoietic cell types. Here we report for the first time that CD45-/- bone marrow dendritic cells (BMDC) are more activated than CD45+/+ cells and that tumour necrosis factor (TNF) and interleukin-6 (IL-6) production by BMDC and splenic dendritic cells (sDC), is increased following stimulation via Toll-like receptor (TLR)3 and TLR9. Nuclear factor-kappaB activation, an important downstream consequence of TLR3 and TLR9 signalling, is also increased in CD45-/- BMDC. BMDC of CD45-/- mice also produce more TNF and IL-6 following stimulation with the cytokines TNF and interferon-alpha. These results show that TLR signalling is increased in CD45-/- dendritic cells and imply that CD45 is a negative regulator of TLR and cytokine receptor signalling in dendritic cells.
Piercy
Jenny
J
The Edward Jenner Institute for Vaccine Research, Compton, Berkshire RG20 7NN, UK.
Petrova
Svetla
S
Tchilian
Elma Z
EZ
Beverley
Peter C L
PC
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007369:Interferon Inducers / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016207:Cytokines; D007369:Interferon Inducers; D015850:Interleukin-6; D016328:NF-kappa B; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens; D011070:Poly I-C