The role of Jak 2 and Stat 5 in antigen-induced eosinophil recruitment into the airways

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We studied the role of Jak 2 and Stat 5 in antigen-induced eosinophil recruitment into the airways of sensitized mice. The in vivo administration of a Jak 2 inhibitor AG-490 prevented antigen induced eosinophil recruitment into the airways of sensitized mice in a dose-dependent manner, whereas the administration of AG-490 did not affect antigen induced IL-5 production in the airways. On the other hand, both antigen induced IL -5 production and antigen induced airway eosinophilia was diminished in Stat 5 a-deficient (Stat 5 a-/-) mice and Stat 5 b-deficient (Stat 5 b-/-) mice. In addition, eosinophilopoiesis induced by the administration of recombinant IL-5 was diminished in Stat 5 a-/- mice and Stat 5 b-/- mice. Interestingly, antigen-induced Th 2 cell differentiation was decreased but antigen-induced Th 1 cell differentiation was increased in Stat 5 a-/- mice. Together, these results indicate that Jak 2 and Stat 5 activation are essential for the induction of IL-5-dependent, antigen-induced eosinophil recruitment into the airways and that the defects in antigen induced eosinophil recruitment in Stat 5 a-/- mice and Stat 5 b-/- mice result from both impaired IL -5 production in the airways and diminished IL -5 responsiveness of eosinophils.
日本炎症・再生医学会の論文