JAK3 inhibition, a viable new modality of immunosuppression for solid organ transplants

• Published in: Trends in molecular medicine Vol. 10; no. 11; pp. 532 - 541
• Main Authors: Borie, Dominic C., O'Shea, John J., Changelian, Paul S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2004
• Subjects: Animals; Drug Design; Graft Rejection - prevention & control; Graft Rejection - therapy; Humans; Immunosuppression; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Janus Kinase 3; Lymphocytes - drug effects; Lymphocytes - immunology; Organ Transplantation; Piperidines; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrimidines - pharmacology; Pyrroles - pharmacology; Severe Combined Immunodeficiency - genetics; Transplantation Immunology; Transplantation, Homologous
• ISSN: 1471-4914; 1471-499X
• 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 γ-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.