TY - JOUR
T1 - TLR ligands can activate dendritic cells to provide a MyD88-dependent negative signal for Th2 cell development
AU - Sun, Jie
AU - Walsh, Matthew
AU - Villarino, Alejandro V.
AU - Cervi, Laura
AU - Hunter, Christopher A.
AU - Choi, Yongwon
AU - Pearce, Edward J.
PY - 2005/1/15
Y1 - 2005/1/15
N2 - During infection, CD4+ Th cell responses polarize to become primarily Th1 or Th2. Th1 cells, which make IFN-γ, are crucial for immunity to many bacterial and protozoal infections, whereas Th2 cells, which make IL-4, IL-5, and IL-13, are important for resistance to helminth infections. Polarized Th1 responses are induced by dendritic cells (DCs), which respond to pathogen-derived TLR ligands to produce IL-12 and related cytokines that are instrumental in Th1 cell outgrowth, and coordinately process and present Ag in the context of MHC class II to activate naive Th cells. In this study we show that in addition to providing positive signals for Th1 cell development, mouse DCs activated by TLR engagement can also provide a potent negative signal that prevents the development of Th2 cells. Production of this signal, which is not IL-12, IL-18, IL-23, IL-27, or IFN-γ and is not provided via Th1 cells, is dependent upon a MyD88-dependent, TNF receptor-associated factor-6-independent signaling pathway in DCs. The signal is released from DCs in response to activation via TLR ligands and exerts an effect directly on Th cells rather than through a third-party cell. Our findings indicate that DCs can provide potent negative as well as positive instruction for Th response polarization, and that these instructional signals are distinct and independent.
AB - During infection, CD4+ Th cell responses polarize to become primarily Th1 or Th2. Th1 cells, which make IFN-γ, are crucial for immunity to many bacterial and protozoal infections, whereas Th2 cells, which make IL-4, IL-5, and IL-13, are important for resistance to helminth infections. Polarized Th1 responses are induced by dendritic cells (DCs), which respond to pathogen-derived TLR ligands to produce IL-12 and related cytokines that are instrumental in Th1 cell outgrowth, and coordinately process and present Ag in the context of MHC class II to activate naive Th cells. In this study we show that in addition to providing positive signals for Th1 cell development, mouse DCs activated by TLR engagement can also provide a potent negative signal that prevents the development of Th2 cells. Production of this signal, which is not IL-12, IL-18, IL-23, IL-27, or IFN-γ and is not provided via Th1 cells, is dependent upon a MyD88-dependent, TNF receptor-associated factor-6-independent signaling pathway in DCs. The signal is released from DCs in response to activation via TLR ligands and exerts an effect directly on Th cells rather than through a third-party cell. Our findings indicate that DCs can provide potent negative as well as positive instruction for Th response polarization, and that these instructional signals are distinct and independent.
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U2 - 10.4049/jimmunol.174.2.742
DO - 10.4049/jimmunol.174.2.742
M3 - Article
C2 - 15634894
AN - SCOPUS:11844305672
SN - 0022-1767
VL - 174
SP - 742
EP - 751
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -