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- Title
Src Kinases Are Required for a Balanced Production of IL-12/IL-23 in Human Dendritic Cells Activated by Toll-Like Receptor Agonists.
- Authors
Kuka, Mirela; Baronio, Roberta; Valentini, Sara; Monaci, Elisabetta; Muzzi, Alessandro; Aprea, Susanna; Gregorio, Ennio De; D'Oro, Ugo
- Abstract
Background: 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. Principal Findings: In this work we investigated the role of Src kinases during different TLRs triggering in human monocytederived 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 to promote the Th17 subset survival but are less efficient in inducing Th1 differentiation. Conclusions: We suggest that the pharmacological modulation of DC maturation has the potential to shape the quality of the adaptive immune response and could be exploited for the treatment of inflammation-related diseases.
- Subjects
DENDRITIC cells; IMMUNE response; T cells; ENZYME inhibitors; CYTOKINES; ANTIGENS; CELL culture; FLOW cytometry; CELL receptors; DNA microarrays; CELL proliferation
- Publication
PLoS ONE, 2010, Vol 5, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0011491