REPORT

New targets I—signal transduction

Targeting the Jak/STAT pathway for immunosuppression

J J O’Shea

Correspondence to:
Correspondence to:
J J O’Shea
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA; osheajo@mail.nih.gov

Abbreviations: Jaks, Janus kinases; IL, interleukin; NK, natural killer; SCID, severe combined immunodeficiency; STAT, signal transducer and activator of transcription; Th, T helper

Keywords: Janus kinases; Jaks; STATs; signal transducer and activator of transcription; immunosuppression; cyokine signalling

The first 150 words of the full text of this article appear below.

While many effective immunosuppressive drugs exist and are in wide use, most target ubiquitously expressed molecules. Examples include steroids, ciclosporin A, tacrolimus, mycophenolate mofetil, and sirolimus. Consequently, these drugs have adverse effects unrelated to their immunosuppressive actions, and much effort has been directed towards identifying molecular targets with expression restricted to immune and inflammatory cells. In principle, such drugs could provide immunosuppression yet lack the toxicity associated with current therapies.

It is now well established that cytokines have critical roles in regulating immunity and inflammation; indeed targeting cytokines themselves has been an effective new strategy for immunosuppression.¹ However, targeting intracellular cytokine signalling also now appears to be a viable new approach. Janus kinases (Jaks) and signal transducers and activators of transcription (STATs) have been demonstrated to be critical elements in signalling by certain families of cytokines. Importantly, the generation of a selective inhibitor of Jak3 appears . . . [Full text of this article]

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