Research ArticleImmunology

Distinct Signal Codes Generate Dendritic Cell Functional Plasticity

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Sci. Signal.  19 Jan 2010:
Vol. 3, Issue 105, pp. ra4
DOI: 10.1126/scisignal.2000567

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Our adaptive immune system induces distinct responses to different pathogens because of the functional plasticity of dendritic cells (DCs); however, how DCs program unique responses remains unclear. Here, we found that the cytokine thymic stromal lymphopoietin (TSLP) potently transduced a unique T helper type 2 (TH2)–inducing compound signal in DCs. Whereas activation of nuclear factor κB (predominantly p50) drove DCs to produce OX40L to induce TH2 differentiation, the activation of signal transducer and activator of transcription 6 (STAT6) triggered DCs to secrete chemokines necessary for the recruitment of TH2 cells. In addition, TSLP signaling limited the activation of STAT4 and interferon regulatory factor 8 (IRF-8), which are essential factors for the production of the TH1-polarizing cytokine interleukin-12 (IL-12). By contrast, Toll-like receptor ligands and CD40 ligand did not activate STAT6 in myeloid DCs, but instead increased the abundance of STAT4 and IRF-8 to induce TH1 responses through the production of IL-12. Therefore, we propose that the functional plasticity of DCs relies on elaborate signal codes that are generated by different stimuli.

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