Borie Dominic C, O'Shea John J, Changelian Paul S
Transplantation Immunology Laboratory, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305-5407, USA.
Trends Mol Med. 2004 Nov;10(11):532-41. doi: 10.1016/j.molmed.2004.09.007.
The field of organ transplantation has had tremendous success because of the availability of immunosuppressive drugs that efficiently prevent acute organ rejection. Numerous and severe side effects are, however, associated with all current immunosuppressive therapies and justify a search for drugs with better efficacy and safety profiles. Janus kinase (JAK) 3, a tyrosine kinase that is crucial for mediating signals from the common gamma-chain of cytokine receptors, is peculiar in that its expression, contrarily to the targets of most current immunosuppressive drugs, is limited to cells that actively participate to the immune response to allografts. The recent demonstration in stringent preclinical models that JAK3 inhibition results in efficacy for the prevention of allograft rejection with a narrow side-effect profile might lead to a new era in the field of immunosuppression.
由于有能有效预防急性器官排斥反应的免疫抑制药物，器官移植领域取得了巨大成功。然而，目前所有的免疫抑制疗法都伴有众多严重的副作用，这使得人们有理由去寻找疗效和安全性更好的药物。 Janus激酶（JAK）3是一种酪氨酸激酶，对介导细胞因子受体共同γ链发出的信号至关重要，其独特之处在于，与目前大多数免疫抑制药物的靶点不同，它的表达仅限于积极参与同种异体移植免疫反应的细胞。最近在严格的临床前模型中证明，抑制JAK3能有效预防同种异体移植排斥反应且副作用较小，这可能会开创免疫抑制领域的新纪元。
