Deletion of Slam locus in mice reveals inhibitory role of SLAM family in NK cell responses regulated by cytokines and LFA-1.
Deletion of Slam locus in mice reveals inhibitory role of SLAM family in NK cell responses regulated by cytokines and LFA-1.
复制标题
DOI：
10.1084/jem.20160552
复制
发表时间：
2016-09-19
期刊：
影响因子：
--
通讯作者：
Veillette A
中科院分区：
文献类型：
--
作者：
Guo H;Cranert SA;Lu Y;Zhong MC;Zhang S;Chen J;Li R;Mahl SE;Wu N;Davidson D;Waggoner SN;Veillette A
Veillette及其合作者生成了一个小鼠模型，该模型在1号染色体上缺失了整个400 kb的Slam基因座，以显示SLAM蛋白在NK细胞发育和功能中的整体作用。信号淋巴细胞活化分子（SLAM）家族受体（SFR）在自然杀伤细胞（NK细胞）活化过程中可介导活化或抑制作用。在这项研究中，我们通过分析一只缺乏完整的SLAM 400-SLAM酶Slam基因座的小鼠，解决了SLAM家族在NK细胞中的全球作用、调节和作用机制，该基因座编码所有六种SFR和CD 48，SFR 2B 4的配体。该小鼠表现出对造血靶细胞的增强的NK细胞活化应答。对缺乏单个SFR的小鼠的分析表明，Slam基因座的抑制功能仅归因于2B 4，并且不受其他SFR的积极或消极影响。表达或缺乏SFR配体的靶标识别之间的NK细胞应答差异被IL-12增强，但被I型干扰素抑制。细胞因子还改变了SLAM相关蛋白衔接子的水平，这阻止了SFR的抑制功能。SFR缺陷的NK细胞的增强的活化应答依赖于整合素LFA-1，而不依赖于DNAM-1或NKG 2D。SFR介导的抑制阻止了LFA-1的活化形式的产生。因此，Slam基因座在NK细胞活化过程中具有完全依赖于2B 4的总体抑制作用。这种作用受到细胞因子的影响，并导致LFA-1活性的抑制。
Veillette and collaborators generate a mouse model with a deletion spanning the entire 400-kb Slam locus on chromosome 1 to show the overall role of SLAM proteins in NK cell development and function. Signaling lymphocytic activation molecule (SLAM) family receptors (SFRs) can mediate either activating or inhibitory effects during natural killer cell (NK cell) activation. In this study, we addressed the global role, regulation, and mechanism of action of the SLAM family in NK cells by analyzing a mouse lacking the entire ∼400-kilobase Slam locus, which encodes all six SFRs and CD48, the ligand of SFR 2B4. This mouse displayed enhanced NK cell activation responses toward hematopoietic target cells. Analyses of mice lacking individual SFRs showed that the inhibitory function of the Slam locus was due solely to 2B4 and was not influenced positively or negatively by other SFRs. Differences in NK cell responses between recognition of targets expressing or lacking ligands for SFRs were enhanced by IL-12 but suppressed by type I interferon. Cytokines also changed the levels of SLAM-associated protein adaptors, which prevent the inhibitory function of SFRs. The enhanced activation responses of SFR-deficient NK cells were dependent on integrin LFA-1 but not on DNAM-1 or NKG2D. SFR-mediated inhibition prevented the generation of activated forms of LFA-1. Hence, the Slam locus has an overall inhibitory role during NK cell activation that is solely dependent on 2B4. This effect is influenced by cytokines and leads to suppression of LFA-1 activity.
登录
查看更多内容
受体LY108充当SAP适应器依赖性的开关开关，可帮助B细胞和NKT细胞发育。
影响因子：
32.4
作者：
Kageyama R;Cannons JL;Zhao F;Yusuf I;Lao C;Locci M;Schwartzberg PL;Crotty S
通讯作者：
Crotty S
DOI：
10.1084/jem.192.3.337
发表时间：
2000-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Parolini S;Bottino C;Falco M;Augugliaro R;Giliani S;Franceschini R;Ochs HD;Wolf H;Bonnefoy JY;Biassoni R;Moretta L;Notarangelo LD;Moretta A
通讯作者：
Moretta A
2B4 作为小鼠自然杀伤细胞上的非主要组织相容性复合物结合抑制受体。
DOI：
10.1084/jem.20031989
发表时间：
2004-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee KM;McNerney ME;Stepp SE;Mathew PA;Schatzle JD;Bennett M;Kumar V
通讯作者：
Kumar V
统一依赖MHC的天然杀手细胞教育的概念。
影响因子：
16.8
作者：
Elliott JM;Yokoyama WM
通讯作者：
Yokoyama WM
影响因子：
7.3
作者：
Marçais A;Viel S;Grau M;Henry T;Marvel J;Walzer T
通讯作者：
Walzer T