Src kinases are required for a balanced production of IL-12/IL-23 in human dendritic cells activated by Toll-like receptor agonists.

PloS One
Mirela KukaUgo D'Oro

Abstract

Pathogen recognition by dendritic cells (DC) is crucial for the initiation of both innate and adaptive immune responses. Activation of Toll-like Receptors (TLRs) by microbial molecular patterns leads to the maturation of DC, which present the antigen and activate T cells in secondary lymphoid tissues. Cytokine production by DC is critical for shaping the adaptive immune response by regulating T helper cell differentiation. It was previously shown by our group that Src kinases play a key role in cytokines production during TLR4 activation in human DC. In this work we investigated the role of Src kinases during different TLRs triggering in human monocyte-derived DC (MoDC). We found that Src family kinases are important for a balanced production of inflammatory cytokines by human MoDC upon stimulation of TLR3 and 8 with their respective agonists. Disruption of this equilibrium through pharmacological inhibition of Src kinases alters the DC maturation pattern. In particular, while expression of IL-12 and other inflammatory cytokines depend on Src kinases, the induction of IL-23 and co-stimulatory molecules do not. Accordingly, DC treated with Src inhibitors are not compromised in their ability to induce CD4 T cell proliferation and...Continue Reading

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Citations

Jan 10, 2013·Glycoconjugate Journal·Maria A SouzaMaria Cristina Roque-Barreira
Nov 22, 2014·Phytotherapy Research : PTR·To Thi Mai DungJae Youl Cho
May 1, 2017·Molecular Nutrition & Food Research·Weiqun LinWenhua Ling

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Datasets Mentioned

BETA
GM-CSF
E-TABM-1018

Methods Mentioned

BETA
flow cytometry
ELISA
Assay
Protein Assay

Software Mentioned

Flowjo
NanoDrop
BASE
Mesoscale
DIVA
Image J
GenePix

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