Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3.
Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3.
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DOI：
10.1084/jem.187.12.2009
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发表时间：
1998-06-15
期刊：
影响因子：
--
通讯作者：
Neote K
中科院分区：
文献类型：
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作者：
Cole KE;Strick CA;Paradis TJ;Ogborne KT;Loetscher M;Gladue RP;Lin W;Boyd JG;Moser B;Wood DE;Sahagan BG;Neote K
趋化因子是正常白细胞运输以及炎症期间白细胞募集的必需介质。我们在这里描述了一种新的非ELR CXC趋化因子，通过序列分析的cDNA来源于精氨酸激活的原代人星形胶质细胞。这种新的趋化因子，称为I-TAC（干扰素诱导T细胞α趋化因子），受干扰素（IFN）调节，对白细胞介素（IL）-2激活的T细胞具有强效趋化活性，但对新鲜分离的未刺激的T细胞，中性粒细胞或单核细胞不具有趋化活性。I-TAC选择性地与CXCR 3相互作用，CXCR 3是另外两种IFN诱导型趋化因子的受体，IFN-γ诱导型10-kD蛋白（IP-10）和IFN-γ诱导型人单核因子（HuMig），但具有显著更高的亲和力。此外，通过在活化的T细胞和表达CXCR 3的转染细胞系中瞬时动员细胞内钙以及趋化性迁移，证明了I-TAC的效力和功效高于IP-10和HuMig。用IFN-γ和IL-1一起刺激星形胶质细胞导致I-TAC mRNA表达增加1000，000倍，而用单独或组合的细胞因子刺激单核细胞仅导致I-TAC转录物水平增加100倍。在胰腺、肺、胸腺和脾脏中也观察到中度表达。在IFN-和IL-1刺激的星形胶质细胞中的高水平表达表明，I-TAC可能是参与神经炎性疾病的病理生理学的效应T细胞的主要化学引诱物，尽管I-TAC也可能在IFN主导的免疫应答期间活化T细胞的迁移中发挥作用。
Chemokines are essential mediators of normal leukocyte trafficking as well as of leukocyte recruitment during inflammation. We describe here a novel non-ELR CXC chemokine identified through sequence analysis of cDNAs derived from cytokine-activated primary human astrocytes. This novel chemokine, referred to as I-TAC (interferon-inducible T cell alpha chemoattractant), is regulated by interferon (IFN) and has potent chemoattractant activity for interleukin (IL)-2–activated T cells, but not for freshly isolated unstimulated T cells, neutrophils, or monocytes. I-TAC interacts selectively with CXCR3, which is the receptor for two other IFN-inducible chemokines, the IFN-γ–inducible 10-kD protein (IP-10) and IFN-γ– induced human monokine (HuMig), but with a significantly higher affinity. In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig is demonstrated by transient mobilization of intracellular calcium as well as chemotactic migration in both activated T cells and transfected cell lines expressing CXCR3. Stimulation of astrocytes with IFN-γ and IL-1 together results in an ∼400,000-fold increase in I-TAC mRNA expression, whereas stimulating monocytes with either of the cytokines alone or in combination results in only a 100-fold increase in the level of I-TAC transcript. Moderate expression is also observed in pancreas, lung, thymus, and spleen. The high level of expression in IFN- and IL-1–stimulated astrocytes suggests that I-TAC could be a major chemoattractant for effector T cells involved in the pathophysiology of neuroinflammatory disorders, although I-TAC may also play a role in the migration of activated T cells during IFN-dominated immune responses.