Abstract
Regulation of T cell homeostasis is critical for maintaining normal immune function. An imbalance in T cell proliferation can result in disorders ranging from cancer and autoimmunity to immunodeficiencies. Full activation of T cells requires three sequential signals, where signal 3, which is delivered by multiple cytokines, regulates proliferation, differentiation, and survival/death. Signaling from cytokines through their receptors is primarily delivered by two molecular families, namely Janus tyrosine kinases (JAKs) and signal transducers and activators of transcription (STATs). Invaluable knowledge about JAKs and STATs has arisen from studies of mice made genetically deficient in these molecules, analyses of tumor models, and studies of expression patterns by proteomics/genomics, which all have begun to define the role of JAKs and STATs in survival versus apoptosis. These findings also have suggested ways in which JAKs and STATs may be manipulated for therapeutic intervention in lymphoid-derived diseases. This review seeks to focus on the role of JAK tyrosine kinases and STAT transcription factors in mediating the lymphocyte life cycle and how they might be manipulated for therapeutic applications.
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Abbreviations
- a.a.:
-
amino-acid
- CaN:
-
calcineurin
- CsA:
-
cyclosporine
- DC:
-
dendritic cells
- γ c :
-
common cytokine receptor γ chain
- EPO:
-
erythropoietin
- FERM domain:
-
Band 4.1, Ezrin, Radixin and Moesin
- IFN:
-
interferon
- IL:
-
interleukin
- JAK:
-
Janus tyrosine kinase
- JH:
-
JAK homological
- MAb:
-
monoclonal antibody
- mTOR:
-
mammalian target of rapamycin
- Pias:
-
protein inhibitor of activated STAT
- PI3k:
-
phosphatidyl inositol 3-kinase
- PMSP:
-
Proline Methionine Serine Proline (Pro-Met-Ser-Pro)
- PSP:
-
Proline Serine Proline (Pro-Ser-Pro)
- RAPA:
-
rapamycin
- SP:
-
Serine Proline (Ser-Pro)
- SCID:
-
severe combined immunodeficiency disease
- SH2:
-
src homology domain 2
- SHP:
-
SH2 containing tyrosine phosphatase
- SOCS:
-
suppressor of cytokine signaling
- STAT:
-
signal transducer and activator of transcription
- TCGF:
-
T cell growth factors
- TCR:
-
T cell receptor
- Th:
-
T-helper
- Treg:
-
T regulatory
- PHA:
-
phytohemagglutinin
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Ross, J.A., Nagy, Z.S., Cheng, H. et al. Regulation of T cell homeostasis by JAKs and STATs. Arch. Immunol. Ther. Exp. 55, 231–245 (2007). https://doi.org/10.1007/s00005-007-0030-x
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DOI: https://doi.org/10.1007/s00005-007-0030-x