SHIP Influences Signals from CD48 and MHC Class I Ligands That Regulate NK Cell Homeostasis, Effector Function, and Repertoire Formation
作者： Nicole R. Fortenbery , Kim H. T. Paraiso , Masaru Taniguchi , Colin Brooks , Leina Ibrahim
关键词: Biology 、 Cell biology 、 NKG2D 、 Immunology 、 CD48 、 MHC class I 、 Receptor 、 Major histocompatibility complex 、 Interleukin 12 、 Interleukin 21 、 Cytolysis
摘要: Previously, we showed that 2B4 is a dominant inhibitory receptor in SHIP-deficient NK cells prevents efficient cytolysis of complex targets. We show this study deficiency restores homeostatic control and cytolytic function to cells. However, 2B4(-/-)SHIP(-/-) still exhibit profound disruption their repertoire are compromised for induction IFN-gamma by several NK-activating receptors, including NKp46, NK.1.1, NKG2D. In addition, find 2B4(-/-) have an extensively disrupted repertoire, supernormal frequency NKp46(+) Consequently induced on much higher percentage following engagement NKp46. also both SHIP required prevent expression Ly49B, myeloid lineage MHC class I not normally expressed the lineage. Finally, when H-2(d) background, they levels Ly49A possess normal against MHC-matched tumor targets enhanced mismatched despite or elevated function, H2d SHIP(-/-) poor like H2b(+) counterparts, demonstrating uniform requirement downstream key activating receptors. These findings reveal interplay SHIP, 2B4, regulation homeostasis, effector formation cell
jimmunol.org 参考文章(47)
Subramaniam Malarkannan, Jeyarani Regunathan, Haiyan Chu, Snjezana Kutlesa, Yuhong Chen, Hu Zeng, Renren Wen, Demin Wang, Bcl10 Plays a Divergent Role in NK Cell-Mediated Cytotoxicity and Cytokine Generation Journal of Immunology. ,vol. 179, pp. 3752- 3762 ,(2007) , 10.4049/JIMMUNOL.179.6.3752
Dawn M. Tanamachi, Deborah C. Moniot, Dragana Cado, Scot D. Liu, Jennifer K. Hsia, David H. Raulet, Genomic Ly49A Transgenes: Basis of Variegated Ly49A Gene Expression and Identification of a Critical Regulatory Element Journal of Immunology. ,vol. 172, pp. 1074- 1082 ,(2004) , 10.4049/JIMMUNOL.172.2.1074
M Manoussaka, J A Toomey, P V Sivakumar, M Bennett, C G Brooks, S Shrestha, A Georgiou, B Rossiter, V Kumar, Phenotypic and functional characterization of long-lived NK cell lines of different maturational status obtained from mouse fetal liver. Journal of Immunology. ,vol. 158, pp. 112- 119 ,(1997)
Vanessa L. Ott, Idan Tamir, Masaru Niki, Pier Paolo Pandolfi, John C. Cambier, Downstream of Kinase, p62dok, Is a Mediator of FcγRIIB Inhibition of FcεRI Signaling Journal of Immunology. ,vol. 168, pp. 4430- 4439 ,(2002) , 10.4049/JIMMUNOL.168.9.4430
Joseph A. Wahle, Kim H. T. Paraiso, Amy L. Costello, Emily L. Goll, Charles L. Sentman, William G. Kerr, Cutting Edge: Dominance by an MHC-Independent Inhibitory Receptor Compromises NK Killing of Complex Targets Journal of Immunology. ,vol. 176, pp. 7165- 7169 ,(2006) , 10.4049/JIMMUNOL.176.12.7165
Léonardo Scarpellino, Franziska Oeschger, Philippe Guillaume, Jérôme D. Coudert, Frédéric Lévy, Georges Leclercq, Werner Held, Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis Journal of Immunology. ,vol. 178, pp. 1277- 1284 ,(2007) , 10.4049/JIMMUNOL.178.3.1277
L A Holmberg, B A Miller, K A Ault, The effect of natural killer cells on the development of syngeneic hematopoietic progenitors. Journal of Immunology. ,vol. 133, pp. 2933- 2939 ,(1984)
Stephan Gasser, Sandra Orsulic, Eric J. Brown, David H. Raulet, The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor Nature. ,vol. 436, pp. 1186- 1190 ,(2005) , 10.1038/NATURE03884
Grazia Maria Spaggiari, Roberta Carosio, Daniela Pende, Stefania Marcenaro, Paola Rivera, Maria Raffaella Zocchi, Lorenzo Moretta, Alessandro Poggi, NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46. European Journal of Immunology. ,vol. 31, pp. 1656- 1665 ,(2001) , 10.1002/1521-4141(200106)31:6<1656::AID-IMMU1656>3.0.CO;2-V
Werner Held, David H. Raulet, Expression of the Ly49A gene in murine natural killer cell clones is predominantly but not exclusively mono-allelic European Journal of Immunology. ,vol. 27, pp. 2876- 2884 ,(1997) , 10.1002/EJI.1830271120