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Specificity of JAK-kinase inhibition determines impact on human and murine T-cell function

Perner , Florian and Heidel, Florian (2016) Specificity of JAK-kinase inhibition determines impact on human and murine T-cell function. Leukemia, 30 (4). pp. 991-995. ISSN 1476-5551; 0887-6924


Clinical use of Janus-Kinase- (JAK-) inhibitors has significantly improved the therapeutic options for
inflammation driven diseases. Particularly inhibitors of Janus-kinases 1 and 2 are in clinical use and (at least one of them) already approved for certain myeloproliferative neoplasms (MPNs) such as primary myelofibrosis or polycythemia vera. JAKs are essential for cytokine-induced intracellular signaling of lymphocytes and their inactivation leads to impairment of immune cell function. Reduction of T-cell reactivity became evident when treating Graft-versus-Host disease (GvHD) in vivo with the JAK1/2 inhibitor ruxolitinib. Most recent reports have highlighted that ruxolitinib constrains T-cell activation and function in MPN patients. Further clinical indicators of impaired T-cell function are severe infections emerging in JAK-inhibitor treated patients among which herpes virus reactivation, cryptococcus neoformans pneumonia, toxoplasmosis retinitis and disseminated tuberculosis are the most alarming. Ongoing pre-clinical and clinical development of more selective JAK1 or JAK2 inhibitors may offer higher efficacy, however, specificity of JAK inhibition may severely influence the emergence of severe infectious complications. We hypothesized that specificity of Janus-kinase inhibition may severely influence the observed immunosuppressive effects.

Item Type: Article
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45


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