A new modality for immunosuppression: Targeting the JAK/STAT pathway

被引:304
作者
O'Shea, JJ [1 ]
Pesu, M
Borie, DC
Changelian, PS
机构
[1] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA
[2] Stanford Univ, Sch Med, Transplantat Immunol Program, Stanford, CA 94305 USA
[3] Pfizer Global Res & Dev, Dept Antibacterials Immunol & Canc, Groton, CT 06340 USA
关键词
D O I
10.1038/nrd1441
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 0836 [生物工程]; 090102 [作物遗传育种]; 100705 [微生物与生化药学];
摘要
Thousands of organs are transplanted each year and millions of people suffer from autoimmune diseases, which creates a need for an armamentarium of immunosuppressive drugs. Unfortunately, immunosuppressants have unwanted side effects owing, in part, to the fact that they have ubiquitous molecular targets. Cytokines have emerged as important controllers of the immune response, and work during the past decade has identified Janus kinases (JAKs) and signal transducers, and activators of transcription (STATs), as crucial intracellular elements in cytokine signalling. Here, we discuss the potential of the JAK/STAT pathway as a target for new immunosuppressants. In particular, the inhibition of JAK3 seems to be an excellent strategy, because of the selective expression and precise functions of this kinase.
引用
收藏
页码:555 / 564
页数:10
相关论文
共 136 条
[1]
Inhibition of JAK3 induces apoptosis and decreases anaplastic lymphoma kinase activity in anaplastic large cell lymphoma [J].
Amin, HM ;
Medeiros, LJ ;
Ma, Y ;
Feretzaki, M ;
Das, P ;
Leventaki, V ;
Rassidakis, GZ ;
O'Connor, SL ;
McDonnell, TJ ;
Lai, R .
ONCOGENE, 2003, 22 (35) :5399-5407
[2]
[Anonymous], J CLIN INVEST
[3]
Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies:: report of the European experience 1968-99 [J].
Antoine, C ;
Müller, S ;
Cant, A ;
Cavazzana-Calvo, M ;
Veys, P ;
Vossen, J ;
Fasth, A ;
Heilmann, C ;
Wulffraat, N ;
Seger, R ;
Blanche, S ;
Friedrich, W ;
Abinun, M ;
Davies, G ;
Bredius, R ;
Schulz, A ;
Landais, P ;
Fischer, A .
LANCET, 2003, 361 (9357) :553-560
[4]
Cutting edge:: The common γ-chain is an indispensable subunit of the IL-21 receptor complex [J].
Asao, H ;
Okuyama, C ;
Kumaki, S ;
Ishii, N ;
Tsuchiya, S ;
Foster, D ;
Sugamura, K .
JOURNAL OF IMMUNOLOGY, 2001, 167 (01) :1-5
[5]
IL-7-dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL [J].
Barata, JT ;
Boussiotis, VA ;
Yunes, JA ;
Ferrando, AA ;
Moreau, LA ;
Veiga, JP ;
Sallan, SE ;
Look, AT ;
Nadler, LM ;
Cardoso, AA .
BLOOD, 2004, 103 (05) :1891-1900
[6]
A requirement for IL-2/IL-2 receptor signaling in intrathymic negative selection [J].
Bassiri, H ;
Carding, SR .
JOURNAL OF IMMUNOLOGY, 2001, 166 (10) :5945-5954
[7]
Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells [J].
Becker, TC ;
Wherry, EJ ;
Boone, D ;
Murali-Krishna, K ;
Antia, R ;
Ma, A ;
Ahmed, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (12) :1541-1548
[8]
Concomitant inhibition of janus kinase 3 and calcineurin-dependent signaling pathways synergistically prolongs the survival of rat heart allografts [J].
Behbod, F ;
Erwin-Cohen, RA ;
Wang, ME ;
Trawick, BW ;
Qu, X ;
Verani, R ;
Kahan, BD ;
Stepkowski, SM ;
Kirken, RA .
JOURNAL OF IMMUNOLOGY, 2001, 166 (06) :3724-3732
[9]
Molecular phylogeny within type I cytokines and their cognate receptors [J].
Boulay, JL ;
O'Shea, JJ ;
Paul, WE .
IMMUNITY, 2003, 19 (02) :159-163
[10]
PREVENTION OF T-CELL ANERGY BY SIGNALING THROUGH THE GAMMA(C) CHAIN OF THE IL-2 RECEPTOR [J].
BOUSSIOTIS, VA ;
BARBER, DL ;
NAKARAI, T ;
FREEMAN, GJ ;
GRIBBEN, JG ;
BERNSTEIN, GM ;
DANDREA, AD ;
RITZ, J ;
NADLER, LM .
SCIENCE, 1994, 266 (5187) :1039-1042