Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway h

Abstract

Using natural killer T (NKT) cell–deficient mice, we show here that allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma, does not develop in the absence of Vα14i NKT cells. The failure of NKT cell–deficient mice to develop AHR is not due to an inability of these mice to produce type 2 T-helper (Th2) responses because NKT cell–deficient mice that are immunized subcutaneously at non-mucosal sites produce normal Th2-biased responses. The failure to develop AHR can be reversed by the adoptive transfer of tetramer-purified NKT cells producing interleukin (IL)-4 and IL-13 to Ja281−/− mice, which lack the invariant T-cell receptor (TCR) of NKT cells, or by the administration to Cd1d−/− mice of recombinant IL-13, which directly affects airway smooth muscle cells. Thus, pulmonary Vα14i NKT cells crucially regulate the development of asthma and Th2-biased respiratory immunity against nominal exogenous antigens. Therapies that target Vα14i NKT cells may be clinically effective in limiting the development of AHR and asthma.

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Akbari, O., Stock, P., Meyer, E. et al. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med 9, 582–588 (2003). https://doi.org/10.1038/nm851

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