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Publication : iNKT cells require CCR4 to localize to the airways and to induce airway hyperreactivity.

First Author  Meyer EH Year  2007
Journal  J Immunol Volume  179
Issue  7 Pages  4661-71
PubMed ID  17878364 Mgi Jnum  J:152343
Mgi Id  MGI:4358033 Doi  10.4049/jimmunol.179.7.4661
Citation  Meyer EH, et al. (2007) iNKT cells require CCR4 to localize to the airways and to induce airway hyperreactivity. J Immunol 179(7):4661-71
abstractText  iNKT cells are required for the induction of airway hyperreactivity (AHR), a cardinal feature of asthma, but how iNKT cells traffic to the lungs to induce AHR has not been previously studied. Using several models of asthma, we demonstrated that iNKT cells required the chemokine receptor CCR4 for pulmonary localization and for the induction of AHR. In both allergen-induced and glycolipid-induced models of AHR, wild-type but not CCR4-/- mice developed AHR. Furthermore, adoptive transfer of wild-type but not CCR4-/- iNKT cells reconstituted AHR in iNKT cell-deficient mice. Moreover, we specifically tracked CCR4-/- vs wild-type iNKT cells in CCR4-/-:wild-type mixed BM chimeric mice in the resting state, and when AHR was induced by protein allergen or glycolipid. Using this unique model, we showed that both iNKT cells and conventional T cells required CCR4 for competitive localization into the bronchoalveolar lavage/airways compartment. These results establish for the first time that the pulmonary localization of iNKT cells critical for the induction of AHR requires CCR4 expression by iNKT cells.
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