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The role of src-family tyrosine kinases in LPS-induced DC maturation has not been fully addressed. We show that LPS induces activation of c-Src and Lyn in human DC. Inhibition of these kinasesby PP1 uncoupled LPS-induced cytokine production from the up-regulation of costimulatory molecules, resulting in DC still capable of stimulating T cell proliferation but much less efficient in inducing Th1 differentiation. This is the first example of a pharmacological inhibitor able to modulate the capacity of DC to induce a particular type of immune response. Inhibition of src-family kinases impaired phosphorylation and accumulation of c-Jun, leading to reduced formation of AP-1 complexes upon LPS stimulation. Thus, src-kinases control cytokine production in LPS-induced DC maturation through a timely formation of AP-1.

Original publication

DOI

10.1002/eji.200324073

Type

Journal article

Journal

Eur J Immunol

Publication Date

10/2003

Volume

33

Pages

2832 - 2841

Keywords

Cell Differentiation, Cells, Cultured, Cytokines, DNA-Binding Proteins, Dendritic Cells, Enzyme Activation, Humans, Interferon Regulatory Factor-1, Interferon Regulatory Factors, Lipopolysaccharides, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins c-jun, Receptors, CCR7, Receptors, Chemokine, Repressor Proteins, Th1 Cells, Transcription Factor AP-1, Up-Regulation, src-Family Kinases