Research ArticleImmunology

Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response

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Science Signaling  01 Dec 2015:
Vol. 8, Issue 405, pp. ra122
DOI: 10.1126/scisignal.aab0949

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Targeting ITK in asthma

CD4+ T helper 2 (TH2) lymphocytes secrete the cytokines interleukin-4 (IL-4), IL-15, and IL-13, which are implicated in the pathogenesis of asthma. Antigen stimulation of T cells activates the kinase ITK, which is required for TH2-type cytokine production. ITK knockout mice are resistant to airway inflammation, which suggests that ITK inhibitors might be used to treat human asthma. However, Sun et al. found that a mouse model of asthma developed worse disease when treated with an ITK-specific inhibitor, exhibiting increased numbers of T cells and amounts of TH2-type cytokines in the airways. These effects were associated with a failure of ITK-inhibited T cells to undergo antigen-stimulated cell death. Together, these data suggest that targeting the kinase activity of ITK in human asthma may exacerbate disease.