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-kappa B 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.