Distinct signal codes generate dendritic cell functional plasticity.
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 (T(H)2)-inducing compound signal in DCs. Whereas activation of nuclear factor kappaB (predominantly p50) drove DCs to produce OX40L to induce T(H)2 differentiation, the activation of signal transducer and activator of transcription 6 (STAT6) triggered DCs to secrete chemokines necessary for the recruitment of T(H)2 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 T(H)1-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 T(H)1 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.
Arima
Kazuhiko
K
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.
Watanabe
Norihiko
N
Hanabuchi
Shino
S
Chang
Mikyoung
M
Sun
Shao-Cong
SC
Liu
Yong-Jun
YJ
D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D053278:OX40 Ligand / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D016328:NF-kappa B; D053278:OX40 Ligand; D050791:STAT Transcription Factors; C089251:TNFSF4 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D000094632:Thymic Stromal Lymphopoietin