Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

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).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Vitamin D Regulation of OX40 Ligand in Immune Responses to Aspergillus fumigatus.
N. L. H. Nguyen, K. Chen, J. Mcaleer, and J. K. Kolls (2013)
Infect. Immun. 81, 1510-1519
   Abstract »    Full Text »    PDF »
Differences in signaling through the B-cell leukemia oncoprotein CRLF2 in response to TSLP and through mutant JAK2.
D. van Bodegom, J. Zhong, N. Kopp, C. Dutta, M.-S. Kim, L. Bird, O. Weigert, J. Tyner, A. Pandey, A. Yoda, et al. (2012)
Blood 120, 2853-2863
   Abstract »    Full Text »    PDF »
A STATus report on DC development.
H. S. Li and S. S. Watowich (2012)
J. Leukoc. Biol. 92, 445-459
   Abstract »    Full Text »    PDF »
The multiple facets of thymic stromal lymphopoietin (TSLP) during allergic inflammation and beyond.
F. Roan, B. D. Bell, T. A. Stoklasek, M. Kitajima, H. Han, and S. F. Ziegler (2012)
J. Leukoc. Biol. 91, 877-886
   Abstract »    Full Text »    PDF »
TSLP Signaling Network Revealed by SILAC-Based Phosphoproteomics.
J. Zhong, M.-S. Kim, R. Chaerkady, X. Wu, T.-C. Huang, D. Getnet, C. J. Mitchell, S. M. Palapetta, J. Sharma, R. N. O'Meally, et al. (2012)
Mol. Cell. Proteomics 11, M112.017764
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882