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JCI:树突状细胞调节新机制

来源:生物谷 2007-10-24 09:15

    美国科学家近日首次研究发现,人体免疫系统能够同时激活和抑制自然杀伤细胞(NK)的不同免疫响应。这一发现将有助于科学家更深入地研究器官移植排斥反应。相关论文10月18日在线发表于《临床检查杂志》(The  Journal  of  Clinical  Investigation)上。 

    NK细胞能够抵御病毒的入侵,但是它的有效发挥作用需要树突状细胞(DCs)的“刺激”。树突状细胞会附着在NK细胞的表面,激活相关受体,最后这两种细胞之间会形成神经突触以进行交流。一般来说,这些突触是由激活受体或抑制受体组成,可开启或关闭NK细胞。 

    在最新的研究中,美国洛克菲勒大学的Christian  Münz和同事仔细研究了这种突触的结构,结果发现这两种受体同时存在,不过是分别位于突触不同的区域。 

    Münz表示,这是首次发现这种交互作用。这种突触具有新颖的调节机制,两种受体同时发挥作用,调节激活和抑制信号。树突状细胞向NK细胞释放不同的信号,抑制了它们杀伤或溶解细胞的功能,同时却激活它们进行分化,释放出细胞素信号分子并转变成更强的“杀手”。 

    Münz表示,目前的研究只是初级阶段。由于树突状细胞与T细胞之间也存在联系,所以下一步将会深入研究T细胞激活的生物学机制。将来如果能找到一种方法阻止NK细胞识别树突状细胞,将有可能阻止树突状细胞激活人体免疫系统,使其不会对移植器官产生攻击反应。(科学网  梅进/编译) 

    (《临床检查杂志》(The  Journal  of  Clinical  Investigation),doi:10.1172/JCI31751,Fabienne  Brilot,Christian  Münz)

原始出处:

Published October 18, 2007

J. Clin. Invest. doi:10.1172/JCI31751.

NK cell survival mediated through the regulatory synapse with human DCs requires IL-15Rα

Fabienne Brilot, Till Strowig, Susanne M. Roberts, Frida Arrey and Christian Münz

Laboratory of Viral Immunobiology and Christopher H. Browne Center for Immunology and Immune Diseases, Rockefeller University, New York, New York, USA.

Address correspondence to: Christian Münz, Laboratory of Viral Immunobiology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. Phone: (212) 327-7611; Fax: (212) 327-7887; E-mail: munzc@rockefeller.edu.

Received for publication February 8, 2007, and accepted in revised form August 15, 2007.

DCs activate NK cells during innate immune responses to viral infections. However, the composition and kinetics of the immunological synapse mediating this interaction are largely unknown. Here, we report the rapid formation of an immunological synapse between human resting NK cells and mature DCs. Although inhibitory NK cell receptors were polarized to this synapse, where they are known to protect mature DCs from NK cell lysis, the NK cell also received activation signals that induced mobilization of intracellular calcium and CD69 upregulation. The high-affinity component of the receptor for IL-15, IL-15Rα, accumulated at the synapse center on NK cells, and blocking of IL-15Rα increased NK cell apoptosis and diminished NK cell survival during their interaction with DCs. Furthermore, IL-15Rα–deficient NK cells, obtained from donors with a history of infectious mononucleosis, showed diminished survival in culture with DCs. Synapse formation was required for IL-15Rα–mediated NK cell survival, because synapse disruption by adhesion molecule blocking decreased DC-induced NK cell survival. These results identify what we believe to be a novel regulatory NK cell synapse with hallmarks of spatially separated inhibitory and activating interactions at its center. We suggest that this synapse formation enables optimal NK cell activation by DCs during innate immune responses.

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