| First Author | Sun Y | Year | 2015 |
| Journal | Sci Signal | Volume | 8 |
| Issue | 405 | Pages | ra122 |
| PubMed ID | 26628680 | Mgi Jnum | J:259522 |
| Mgi Id | MGI:6141945 | Doi | 10.1126/scisignal.aab0949 |
| Citation | Sun Y, et al. (2015) Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response. Sci Signal 8(405):ra122 |
| abstractText | Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and decreased amounts of TH2-type cytokines in the bronchoalveolar lavage fluid. We found that a small-molecule selective inhibitor of ITK blocked TCR-mediated signaling in cultured TH2 cells, including the tyrosine phosphorylation of phospholipase C-gamma1 (PLC-gamma1) and the secretion of IL-2 and TH2-type cytokines. Unexpectedly, inhibition of the kinase activity of ITK during or after antigen rechallenge in an ovalbumin-induced mouse model of asthma failed to reduce airway hyperresponsiveness and inflammation. Rather, in mice, pharmacological inhibition of ITK resulted in T cell hyperplasia and the increased production of TH2-type cytokines. Thus, our studies predict that inhibition of the kinase activity of ITK may not be therapeutic in patients with asthma. |
