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Sci. Signal., 19 January 2010
Vol. 3, Issue 105, p. ra4
[DOI: 10.1126/scisignal.2000567]

RESEARCH ARTICLES

Distinct Signal Codes Generate Dendritic Cell Functional Plasticity

Kazuhiko Arima, Norihiko Watanabe*, Shino Hanabuchi, Mikyoung Chang, Shao-Cong Sun, and Yong-Jun Liu{dagger}

Department of Immunology and Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, 7455 Fannin, Unit 901, Houston, TX 77030, USA.

* Present address: Center for Innovation in Immunoregulative Technology and Therapeutics and Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

Abstract: 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 {kappa}B (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.

{dagger} To whom correspondence should be addressed. E-mail: yjliu{at}mdanderson.org

Citation: K. Arima, N. Watanabe, S. Hanabuchi, M. Chang, S.-C. Sun, Y.-J. Liu, Distinct Signal Codes Generate Dendritic Cell Functional Plasticity. Sci. Signal. 3, ra4 (2010).

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