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腾讯登录Blood：提高自然杀伤细胞功能治疗血癌
| 导读 | 斯克里普斯研究所（TRSI）研究人员正在推动发展未来癌症治疗一个强大的工具，用人体的免疫系统来防御疾病。通过揭示一个新的但普遍的细胞信号转导过程，科学家可能已经找到一种方法来操纵免疫系统来更有效地抵御疾病。相关研究论文刊登在<em>Blood</em>杂志上。
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这是一个令人兴奋的发现，因为它可能有助于开发出提高自然杀伤细胞功能... |
斯克里普斯研究所（TRSI）研究人员正在推动发展未来癌症治疗一个强大的工具，用人体的免疫系统来防御疾病。通过揭示一个新的但普遍的细胞信号转导过程，科学家可能已经找到一种方法来操纵免疫系统来更有效地抵御疾病。相关研究论文刊登在<em>Blood</em>杂志上。
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这是一个令人兴奋的发现，因为它可能有助于开发出提高自然杀伤细胞功能的药物。自然杀伤细胞在治疗某些癌症和传染性疾病中已获得的临床效益。自然杀伤细胞能检测癌细胞或病毒感染细胞表面上的特征性改变，通过一个复杂的信号机械最终产生一定的信号使得自然杀伤细胞破坏癌细胞或病毒感染细胞。
相较于其他类型的免疫细胞，自然杀伤细胞能迅速杀死癌细胞。这使得自然杀伤细胞在早期免疫系统免疫反应中非常重要的。然而，到今天为止自然杀伤细胞的疗效是有限的。一个重要瓶颈是要理解抑制自然杀伤细胞功能的机制。近日，Sauer和同事研究揭示了这个难题的关键细节。
此前酶ItpkB作为调节机体免疫功能的一个关键因子，ItpkB主要产生IP4，一个小分子信使，控制其他各种重要的信号分子。IP4可以提高或抑制免疫信号，而这取决于产生IP4的细胞类型。这项新的研究表明缺乏ItpkB的自然杀伤细胞所诱导的免疫信号和功能比表达该酶的自然杀手细胞更强，其结果是小鼠缺乏ItpkB更有效攻击癌细胞。 该研究中还发现了一种化合物可能被用来提高自然杀伤细胞的功能，如果开发成功的话，可用来对抗癌症。
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<img src="http://www.bioon.com/biology/UploadFiles/201211/2012112815305860.gif" alt="" width="115" height="150" border="0" />
<a title="" href="http://dx.doi.org/10.1182/blood-2012-05-429241" target="_blank">doi:10.1182/blood-2012-05-429241</a>
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<br/><strong>Inositol tetrakisphosphate limits NK cell effector functions by controlling phosphoinositide 3-kinase signaling.</strong><br/>
K. Sauer, E. Park, S. Siegemund, A. R. French, J. A. Wahle, L. Sternberg, S. Rigaud, A. H. Jonsson, W. M. Yokoyama, Y. H. Huang
NK cells have important functions in cancer immunosurveillance, bone marrow allograft rejection, fighting infections, tissue homeostasis and reproduction. NK cell-based therapies are promising treatments for blood cancers. Overcoming their currently limited efficacy requires a better understanding of the molecular mechanisms controlling NK cell development and dampening their effector functions. NK cells recognize the loss of self-antigens or upregulation of stress-induced ligands on pathogen-infected or tumor cells through invariant NK cell receptors (NKR), and then kill such stressed cells. Two second-messenger pathways downstream of NKRs are required for NK cell maturation and effector responses: PIP3-generation by PI3K, and generation of diacylglycerol and IP3 by PLCγ. Here, we identify a novel role for the phosphorylated IP3 metabolite inositol(1,3,4,5)tetrakisphosphate (IP4) in NK cells. IP4 promotes NK cell terminal differentiation and acquisition of a mature NKR repertoire. However, in mature NK cells, IP4 limits NKR induced IFNγ secretion, granule exocytosis and target-cell killing, in part by inhibiting the PIP3 effector-kinase Akt. This identifies IP4 as an important novel regulator of NK cell development and function, and expands our understanding of the therapeutically important mechanisms dampening NK cell responses. Our results further suggest that PI3K regulation by soluble IP4 is a broadly important signaling paradigm.
<br/>来源：生物谷
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这是一个令人兴奋的发现，因为它可能有助于开发出提高自然杀伤细胞功能的药物。自然杀伤细胞在治疗某些癌症和传染性疾病中已获得的临床效益。自然杀伤细胞能检测癌细胞或病毒感染细胞表面上的特征性改变，通过一个复杂的信号机械最终产生一定的信号使得自然杀伤细胞破坏癌细胞或病毒感染细胞。
相较于其他类型的免疫细胞，自然杀伤细胞能迅速杀死癌细胞。这使得自然杀伤细胞在早期免疫系统免疫反应中非常重要的。然而，到今天为止自然杀伤细胞的疗效是有限的。一个重要瓶颈是要理解抑制自然杀伤细胞功能的机制。近日，Sauer和同事研究揭示了这个难题的关键细节。
此前酶ItpkB作为调节机体免疫功能的一个关键因子，ItpkB主要产生IP4，一个小分子信使，控制其他各种重要的信号分子。IP4可以提高或抑制免疫信号，而这取决于产生IP4的细胞类型。这项新的研究表明缺乏ItpkB的自然杀伤细胞所诱导的免疫信号和功能比表达该酶的自然杀手细胞更强，其结果是小鼠缺乏ItpkB更有效攻击癌细胞。 该研究中还发现了一种化合物可能被用来提高自然杀伤细胞的功能，如果开发成功的话，可用来对抗癌症。
<div id="ztload">
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201211/2012112815305860.gif" alt="" width="115" height="150" border="0" />
<a title="" href="http://dx.doi.org/10.1182/blood-2012-05-429241" target="_blank">doi:10.1182/blood-2012-05-429241</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Inositol tetrakisphosphate limits NK cell effector functions by controlling phosphoinositide 3-kinase signaling.</strong><br/>
K. Sauer, E. Park, S. Siegemund, A. R. French, J. A. Wahle, L. Sternberg, S. Rigaud, A. H. Jonsson, W. M. Yokoyama, Y. H. Huang
NK cells have important functions in cancer immunosurveillance, bone marrow allograft rejection, fighting infections, tissue homeostasis and reproduction. NK cell-based therapies are promising treatments for blood cancers. Overcoming their currently limited efficacy requires a better understanding of the molecular mechanisms controlling NK cell development and dampening their effector functions. NK cells recognize the loss of self-antigens or upregulation of stress-induced ligands on pathogen-infected or tumor cells through invariant NK cell receptors (NKR), and then kill such stressed cells. Two second-messenger pathways downstream of NKRs are required for NK cell maturation and effector responses: PIP3-generation by PI3K, and generation of diacylglycerol and IP3 by PLCγ. Here, we identify a novel role for the phosphorylated IP3 metabolite inositol(1,3,4,5)tetrakisphosphate (IP4) in NK cells. IP4 promotes NK cell terminal differentiation and acquisition of a mature NKR repertoire. However, in mature NK cells, IP4 limits NKR induced IFNγ secretion, granule exocytosis and target-cell killing, in part by inhibiting the PIP3 effector-kinase Akt. This identifies IP4 as an important novel regulator of NK cell development and function, and expands our understanding of the therapeutically important mechanisms dampening NK cell responses. Our results further suggest that PI3K regulation by soluble IP4 is a broadly important signaling paradigm.
<br/>来源：生物谷
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