Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo
AU - Cook, Peter C
AU - Jones, Lucy H
AU - Jenkins, Stephen J
AU - Wynn, Thomas A
AU - Allen, Judith E
AU - MacDonald, Andrew S
PY - 2012/6/19
Y1 - 2012/6/19
N2 - Interleukin-4 is a cytokine widely known for its role in CD4(+) T cell polarization and its ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on the activation and function of dendritic cells (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro and in vivo by expression of multiple alternative activation markers with a different expression pattern to that of macrophages. We further demonstrate a central role for DC IL-4Rα expression in the optimal induction of IFNγ responses in vivo in both Th1 and Th2 settings, through a feedback loop in which IL-4 promotes DC secretion of IL-12. Finally, we reveal a central role for RELMα during T-cell priming, establishing that its expression by DCs is critical for optimal IL-10 and IL-13 promotion in vitro and in vivo. Together, these data highlight the significant impact that IL-4 and RELMα can have on DC activation and function in the context of either bacterial or helminth pathogens.
AB - Interleukin-4 is a cytokine widely known for its role in CD4(+) T cell polarization and its ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on the activation and function of dendritic cells (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro and in vivo by expression of multiple alternative activation markers with a different expression pattern to that of macrophages. We further demonstrate a central role for DC IL-4Rα expression in the optimal induction of IFNγ responses in vivo in both Th1 and Th2 settings, through a feedback loop in which IL-4 promotes DC secretion of IL-12. Finally, we reveal a central role for RELMα during T-cell priming, establishing that its expression by DCs is critical for optimal IL-10 and IL-13 promotion in vitro and in vivo. Together, these data highlight the significant impact that IL-4 and RELMα can have on DC activation and function in the context of either bacterial or helminth pathogens.
KW - Animals
KW - CD4-Positive T-Lymphocytes
KW - Cell Polarity
KW - Cytokines
KW - Dendritic Cells
KW - Enzyme-Linked Immunosorbent Assay
KW - Flow Cytometry
KW - Humans
KW - In Vitro Techniques
KW - Macrophage Activation
KW - Mice
KW - Mice, Inbred C57BL
KW - Signal Transduction
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1073/pnas.1121231109
DO - 10.1073/pnas.1121231109
M3 - Journal article
C2 - 22660926
VL - 109
SP - 9977
EP - 9982
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 25
ER -