Department of Biology and VCU Allergy and Allergic Disease Cooperative Research Center, Virginia Commonwealth University, Richmond, VA 23284, USA.
Genes Immun. 2010 Dec;11(8):599-608. doi: 10.1038/gene.2010.35. Epub 2010 Jun 10.
The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway mediates important responses in immune cells. Activation of any of the four JAK family members leads to phosphorylation of one or more of seven STAT family members. Phosphorylation of STAT family members leads to their dimerization and translocation into the nucleus, in which they bind specific DNA sequences to activate gene transcription. Regulation of JAKs and STATs therefore has a significant effect on signal transduction and subsequent cellular responses. Mast cells are important mediators of allergic disease and asthma. These cells have the ability to cause profound inflammation and vasodilation upon the release of preformed mediators, as well as subsequent synthesis of new inflammatory mediators. The regulation of mast cells is therefore of intense interest for the treatment of allergic disease. An important regulator of mast cells, STAT5, is activated downstream of the receptors for immunoglobulin E, interleukin-3 and stem cell factor. STAT5 contributes to mast cell homeostasis, by mediating proliferation, survival, and mediator release. Regulators of the JAK-STAT pathway, such as the suppressors of cytokine signaling (SOCS) and protein inhibitor of activated STAT (PIAS) proteins, are required to fine tune the immune response and maintain homeostasis. A better understanding of the role and regulation of JAKs and STATs in mast cells is vital for the development of new therapeutics.
Janus 激酶/信号转导和转录激活因子（JAK-STAT）途径介导免疫细胞中的重要反应。任何四种 JAK 家族成员的激活都会导致一个或多个 STAT 家族成员的磷酸化。STAT 家族成员的磷酸化导致它们二聚化并易位到细胞核内，在细胞核内它们结合特定的 DNA 序列以激活基因转录。因此，JAK 和 STAT 的调节对信号转导和随后的细胞反应有重大影响。肥大细胞是过敏疾病和哮喘的重要介质。这些细胞在释放预先形成的介质以及随后合成新的炎症介质后，具有引起深刻炎症和血管扩张的能力。因此，肥大细胞的调节对于过敏疾病的治疗具有强烈的兴趣。STAT5 是一种重要的肥大细胞调节剂，它是免疫球蛋白 E、白细胞介素-3 和干细胞因子受体下游的激活物。STAT5 通过介导增殖、存活和介质释放来介导肥大细胞的动态平衡。JAK-STAT 途径的调节剂，如细胞因子信号转导抑制物（SOCS）和激活 STAT 的蛋白抑制剂（PIAS）蛋白，是精细调节免疫反应和维持动态平衡所必需的。更好地了解 JAK 和 STAT 在肥大细胞中的作用和调节对于开发新的治疗方法至关重要。
