Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4

Z Mikhak, JP Strassner, AD Luster - Journal of Experimental Medicine, 2013 - rupress.org
Z Mikhak, JP Strassner, AD Luster
Journal of Experimental Medicine, 2013rupress.org
T cell trafficking into the lung is critical for lung immunity, but the mechanisms that mediate T
cell lung homing are not well understood. Here, we show that lung dendritic cells (DCs)
imprint T cell lung homing, as lung DC–activated T cells traffic more efficiently into the lung
in response to inhaled antigen and at homeostasis compared with T cells activated by DCs
from other tissues. Consequently, lung DC–imprinted T cells protect against influenza more
effectively than do gut and skin DC–imprinted T cells. Lung DCs imprint the expression of …
T cell trafficking into the lung is critical for lung immunity, but the mechanisms that mediate T cell lung homing are not well understood. Here, we show that lung dendritic cells (DCs) imprint T cell lung homing, as lung DC–activated T cells traffic more efficiently into the lung in response to inhaled antigen and at homeostasis compared with T cells activated by DCs from other tissues. Consequently, lung DC–imprinted T cells protect against influenza more effectively than do gut and skin DC–imprinted T cells. Lung DCs imprint the expression of CCR4 on T cells, and CCR4 contributes to T cell lung imprinting. Lung DC–activated, CCR4-deficient T cells fail to traffic into the lung as efficiently and to protect against influenza as effectively as lung DC–activated, CCR4-sufficient T cells. Thus, lung DCs imprint T cell lung homing and promote lung immunity in part through CCR4.
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