Sun, 06 Jul 2008 10:56:35 BST CiteULike: AlfonsoVicenteSuarezs ra http://www.citeulike.org/user/AlfonsoVicenteSuarez/tag/ra CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2838041 <i>J Immunol, Vol. 178, No. 7. (1 April 2007), pp. 4548-4556.</i><br /><br />The role of TLRs on intestinal epithelial cells (IECs) is controversial, and the mechanisms by which TLRs influence mucosal homeostasis are obscure. In this study, we report that genomic dsRNA from rotavirus, and its synthetic analog polyinosinic-polycytidylic acid (poly(I:C)), induce severe mucosal injury in the small intestine. Upon engaging TLR3 on IECs, dsRNA triggers IECs to secrete IL-15, which functions to increase the percentage of CD3+NK1.1+ intestinal intraepithelial lymphocytes (IELs) and enhances the cytotoxicity of IELs. Moreover, The CD3+NK1.1+ IELs are proved as CD8alphaalpha+ IELs. These results provide direct evidence that abnormal TLR3 signaling contributes to breaking down mucosal homeostasis and the first evidence of pathogenic effects mediated by CD8alphaalpha+ IELs. The data also suggest that genomic dsRNA may be involved in the pathogenesis of acute rotavirus gastroenteritis. Recognition of Double-Stranded RNA by TLR3 Induces Severe Small Intestinal Injury in Mice Rongbin Zhou Haiming Wei Rui Sun Zhigang Tian J Immunol, Vol. 178, No. 7. (1 April 2007), pp. 4548-4556. 2008-05-27T18:31:42-00:00 2007 J Immunol 178 7 4548 4556 mucosal-immunology ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2829000 <i>Proceedings of the National Academy of Sciences, Vol. 104, No. 18. (1 May 2007), pp. 7512-7515.</i><br /><br />Toll-like receptors (TLRs) and NK receptors are the two most important receptor families in innate immunity. Although it has been observed that TLR signaling can induce or up-regulate the expression of the ligands for stimulatory NK receptors on monocytes or muscle cells, there is not yet a report indicating whether TLR signaling can break down self-tolerance through NK receptors. The present work reports that TLR3 signaling by polyinosinic-polycytidylic acid stimulation induces intestinal epithelial cells (IECs) to express retinoic acid early inducible-1 (a ligand for NKG2D) and to induce NKG2D expression on CD8alphaalpha intestinal intraepithelial lymphocytes by IL-15 derived from TLR3-activated IECs. The blockade of interaction between NKG2D and Rae1 inhibits the cytotoxicity of intraepithelial lymphocytes against IECs in a cell-cell contact-dependent manner and therefore alleviates polyinosinic-polycytidylic acid-induced epithelial destruction and acute mucosal injury of small intestine. These results demonstrate that TLR signaling induces tissue injury through the NKG2D pathway, suggesting that TLR signaling may break down self-tolerance through induction of abnormal expression of ligands for stimulatory NK receptors. 10.1073/pnas.0700822104 NKG2D recognition mediates Toll-like receptor 3 signaling-induced breakdown of epithelial homeostasis in the small intestines of mice Rongbin Zhou Haiming Wei Rui Sun Jian Zhang Zhigang Tian doi:10.1073/pnas.0700822104 Proceedings of the National Academy of Sciences, Vol. 104, No. 18. (1 May 2007), pp. 7512-7515. 2008-05-25T05:03:00-00:00 2007 Proceedings of the National Academy of Sciences 104 18 7512 7515 ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2800416 <i>J. Cell Biol., Vol. 112, No. 5. (1 March 1991), pp. 965-979.</i><br /><br />10.1083/jcb.112.5.965 Overexpression of the cellular retinoic acid binding protein-I (CRABP- I) results in a reduction in differentiation-specific gene expression in F9 teratocarcinoma cells JF Boylan LJ Gudas doi:10.1083/jcb.112.5.965 J. Cell Biol., Vol. 112, No. 5. (1 March 1991), pp. 965-979. 2008-05-15T00:59:11-00:00 1991 J. Cell Biol. 112 5 965 979 crabp ra http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2705497 <i>Int. Immunol., Vol. 19 (October 2007), pp. 1145-1155.</i><br /><br />Monocyte-derived dendritic cells (mDCs) and NK cells are reciprocally activate via cytokines and cellcell contact. Although seven human NKG2D ligands (NKG2DLs), UL16-binding proteins (ULBP) 1, 2, 3 and 4, retinoic acid early transcript 1G (RAET1G) and MHC class I-related chains A and B, have been reported, the differential distribution and roles of these ligands in the maturation of human mDCs have not been elucidated. In the present study, we produced polyclonal antibodies (pAbs) directed against human ULBP1, 2 and 3. All these ULBPs were detected on human mDCs when probed by the pAbs, although their expression profiles were different. We next investigated what kinds of Toll-like receptor agonists and RNA viruses [influenza virus, human respiratory syncytial virus (RSV), measles virus and hepatitis C virus (HCV)] induced the expression of NKG2DLs on mDCs. ULBP1 was up-regulated on mDCs in response to LPS or infection with RSV. The expression of ULBP2 was induced by LPS and poly I:C, indicating that the TIR-containing adapter molecule-1 (TIR domain-containing adaptor-inducing IFN) pathway is associated with ULBP2 induction. Although infection with HCV did not cause up-regulation of NKG2DLs, other RNA virus infections and poly I:C promoted expression of ULBP2 and RAET1G in an IFN-alpha/beta-independent manner. Finally, the over-expression of ULBP1 and 2 on mDCs facilitated NK cell proliferation and IFN-gamma production through a mDCNK cell interaction in the presence of IL-2. Hence, the results reflect the important role of NKG2DLs on human mDCs in mDC-mediated NK cell activation. Induction of NKG2D ligands on human dendritic cells by TLR ligand stimulation and RNA virus infection Takashi Ebihara Hisayo Masuda Takashi Akazawa Masashi Shingai Hideaki Kikuta Tadashi Ariga Misako Matsumoto Tsukasa Seya doi:10.1093/intimm/dxm073 Int. Immunol., Vol. 19 (October 2007), pp. 1145-1155. 2008-04-23T04:48:21-00:00 2007 Int. Immunol. 19 1145 1155 ra http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2255493 <i>Nature Immunology, Vol. 9, No. 2., pp. 119-120.</i> Stress gets under your skin Daniel Andrews Mark Smyth doi:10.1038/ni0208-119 Nature Immunology, Vol. 9, No. 2., pp. 119-120. 2008-01-19T06:11:56-00:00 Nature Immunology 1529-2908 9 2 119 120 Nature Publishing Group ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/329642 <i>Nature Immunology, Vol. 6, No. 10. (04 September 2005), pp. 1011-1019.</i> Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity Christopher Andoniou Serani van Dommelen Valentina Voigt Daniel Andrews Geraldine Brizard Carine Asselin-Paturel Thomas Delale Katryn Stacey Giorgio Trinchieri Mariapia Degli-Esposti doi:10.1038/ni1244 Nature Immunology, Vol. 6, No. 10. (04 September 2005), pp. 1011-1019. 2005-09-22T05:54:07-00:00 2005 Nature Immunology 1529-2908 6 10 1011 1019 Nature Publishing Group ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2782017 <i>Proceedings of the National Academy of Sciences, Vol. 102, No. 31. (2 August 2005), pp. 10846-10851.</i><br /><br />The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8+ T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK- and CD8+ T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines. 10.1073/pnas.0502208102 DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor He Zhou Yunping Luo Jeng-Fan Lo Charles Kaplan Masato Mizutani Noriko Mizutani Jiing-Dwan Lee James Primus Jurgen Becker Rong Xiang Ralph Reisfeld doi:10.1073/pnas.0502208102 Proceedings of the National Academy of Sciences, Vol. 102, No. 31. (2 August 2005), pp. 10846-10851. 2008-05-09T23:48:55-00:00 2005 Proceedings of the National Academy of Sciences 102 31 10846 10851 ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2781997 <i>Cancer Res, Vol. 65, No. 14. (15 July 2005), pp. 6409-6417.</i><br /><br />BCR/ABL fusion gene, encoding a paradigmatic tyrosine kinase involved in chronic myelogenous leukemia (CML), can modulate the expression of genes involved in natural killer (NK) cell target recognition. Recent reports outline the role of allogeneic antileukemic NK effectors in the graft-versus-leukemia effect but the regulation of NK cell activation in the setting of graft-versus-leukemia effect remains unknown. Here we show that dendritic cells derived from monocytes of CML patients are selectively endowed with NK cell stimulatory capacity in vitro. We further show, using a gene transfer approach in mouse bone marrow progenitors, that ABL/ABL is necessary to promote dendritic cell-mediated NK cell activation. The dendritic cell/NK cell cross-talk in ABL/ABL-induced CML seems unique because JunB or IFN consensus sequence binding protein loss of functions, associated with other myeloproliferative disorders, do not promote dendritic cell-mediated NK cell activation. NK cell activation by leukemic dendritic cells involves NKG2D activating receptors and is blocked by imatinib mesylate. Indeed, ABL/ABL translocation enhances the expression levels of the NKG2D ligands on dendritic cells, which is counteracted by imatinib mesylate. Altogether, the clonal ABL/ABL dendritic cells display the unique and selective ability to activate NK cells and may participate in the NK cell control of CML. This study also highlights the deleterious role of imatinib mesylate at the dendritic cell level for NK cell activation. 10.1158/0008-5472.CAN-04-2675 BCR/ABL Promotes Dendritic Cell-Mediated Natural Killer Cell Activation Magali Terme Christophe Borg Francois Guilhot Carole Masurier Caroline Flament Erwin Wagner Sophie Caillat-Zucman Alain Bernheim Ali Turhan Anne Caignard Laurence Zitvogel doi:10.1158/0008-5472.CAN-04-2675 Cancer Res, Vol. 65, No. 14. (15 July 2005), pp. 6409-6417. 2008-05-09T23:33:06-00:00 2005 Cancer Res 65 14 6409 6417 ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1452955 <i>Immunity, Vol. 12, No. 6. (June 2000), pp. 721-727.</i><br /><br />Here we describe a family of GPI-anchored cell surface proteins that function as ligands for the mouse activating NKG2D receptor. These molecules are encoded by the retinoic acid early inducible (RAE-1) and H60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with MHC class I. Expression of the NKG2D ligands is low or absent on normal, adult tissues; however, they are constitutively expressed on some tumors and upregulated by retinoic acid. Ectopic expression of RAE-1 and H60 confers target susceptibility to NK cell attack. These studies identify a family of ligands for the activating NKG2D receptor on NK and T cells, which may play an important role in innate and adaptive immunity. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. A Cerwenka AB Bakker T McClanahan J Wagner J Wu JH Phillips LL Lanier Immunity, Vol. 12, No. 6. (June 2000), pp. 721-727. 2007-07-12T20:32:30-00:00 2000 Immunity 1074-7613 12 6 721 727 ra rae-1