
March 2003 From Journal of Clinical Investigation JCI table of contents, March 3, 2003ONLINE FIRST ARTICLES Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient non obese diabetic mice CONTACT: Christian Boitard INSERM U561 Hopital St. Vincent de Paul 82 Bd Denfert Rochereau 75014 Paris, FRANCE Phone 1: 331-4048-8249 Fax 1: 331-4048-8352 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16584.pdf
TABLE OF CONTENTS IL-12: Bad news for the heart? Myocarditis is associated with viral infections. In addition, several lines of evidence suggest that autoreactive CD8+ T cells play a role in the disease. As IL-12 is part of the innate immune response to viral infections and has been implicated in autoimmune diseases, including myocarditis, Andrew Lichtman and colleagues investigated how IL-12 contributes to the differentiation of T cells that damage the heart. The researchers used a new mouse model of myocarditis that allowed the comparison of different populations of cytotoxic CD8+ T cells specific for the same defined myocardial antigen. Their results (pages 671-680) showed that while IL-12 was not essential for the generation of cytolytic, IFN-g�producing effector T cells, only CD8+ T cells primed in the presence of IL-12 were able to proliferate in vivo and infiltrate the heart in significant numbers. IL-12 thus seems to play an important role in the differentiation of the pathogenic CD8+ T cells that underlie the autoimmune component of myocarditis. CONTACT: Andrew Lichtman Brigham And Women's Hospital Dept. Of Pathology 221 Longwood Ave. Boston, MA 02115-5817 USA Phone 1: 617/732-6532 Fax 1: 617-732-5795 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16867.pdf Therapeutic lymphangiogenesis Mutations in VEGFR-3 cause hereditary lymphedema. While this is a rare disorder, secondary lymphedema, caused by surgical removal of lymph nodes, radiation therapy, or infectious diseases, is a common and disabling condition. Various lines of evidence suggest the potential of the VEGFR-3 ligand VEGF-C for the treatment of lymphedema. Working in two animal models of acute secondary lymphedema, Douglas Losordo and colleagues report (pages 717-725) that local transfer of naked plasmid DNA encoding human VEGF-C promoted lymphangiogenesis and improved physical, functional, and pathologic aspects of the disease in rabbits and mice. Their results also suggest that while plasmid transfer induces only transient expression of VEGF-C, once the lymphatic connection is re-established, drainage function can be maintained. CONTACT: Douglas W. Losordo St. Elizabeth's Medical Center Division of Cardiovascular Research 736 Cambridge Street Boston, MA 02135-2997 USA Phone 1: 617 789-3346 Fax 1: 617-779-6363 Fax 2: 617-779-6362 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15830.pdf ICOS, IL-17, and arthritis ICOS is a costimulator expressed on activated T cells and involved in Th2 function and class switching by B cells. Having previously shown that lack of ICOS enhances the susceptibility in mice to experimental autoimmune encephalomyelitis, Chen Dong and colleagues subsequently examined whether ICOS has a role in rheumatoid arthritis. Working with a well-established mouse model of arthritis, they report (pages 701-706) that in the absence of ICOS, mice normally susceptible to collagen-induced arthritis were completely protected against the disease. ICOS-knockout mice had reduced levels of anti-collagen IgM and IgG antibodies as well as lower levels of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These results warrant additional investigation into the potential of ICOS as a therapeutic target in rheumatoid arthritis. CONTACT: Chen Dong University of Washington Department of Immunology H466 HSC, Box 357650 Seattle, WA 98195 USA Phone 1: 206-221-6694 Fax 1: 206-543-1013 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17321.pdf CD44 and tuberculosis resistance CD44 is an adhesion molecule involved in inflammatory processes. It is present on hematopoietic cells and linked to the cytoskeleton. As cell migration and phagocytosis are dependent on cytoskeletal rearrangements and important in the immune response against Mycobacterium tuberculosis, Jaklien Leemans and colleagues investigated the role of CD44 in pulmonary tuberculosis. Their results (pages 681-689) suggest that CD44 expressed on macrophages is involved in the binding and subsequent uptake of M. tuberculosis. Mice lacking CD44 exhibited a more severe pathological response to infection with M. tuberculosis: they had a profound defect in the early recruitment of macrophages to the lungs, enhanced mycobacterial outgrowth in lung and liver, and a reduced rate of survival compared with controls. CD44 is a unique molecule implicated in the clearance of mycobacteria. CONTACT: Jaklien C. Leemans University of Amsterdam, Academic Medical Center Laboratory of Experimental Internal Medicine Meibergdreef 9 Room G2-105 1105 AZ Amsterdam, THE NETHERLANDS Phone 1: 3120-566-5910 Fax 1: 3120-697-7192 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16936.pdf Mitochondrial mechanotransmission Endothelial cells in the lung generate a proinflammatory response to even modest elevations of vascular pressure. This involves expression of the leukocyte adhesion receptor P-selectin on endothelial cells, which increases leukocyte rolling on the vessel surface. Interested in the underlying mechanisms, Jahar Bhattacharya and colleagues applied real-time, in situ fluorescence microscopy in lung capillaries. As they report (page 691-699), pressure elevation increased the amplitude of cytosolic Ca2+ oscillations, which in turn increased the amplitude of mitochondrial Ca2+ oscillations and the production of reactive oxygen species. P-selectin expression could be inhibited by antioxidants and inhibitors of mitochondrial metabolism, demonstrating that mitochondria are the organelles that couple the mechanical effects of higher pressure to the capillary's proinflammatory response. CONTACT: Jahar Bhattacharya St. Luke's Roosevelt Hospital Center Lung Biology Laboratory St. Luke's-Roosevelt Hospital 1000 Tenth Avenue New York, NY 10019 USA Phone 1: 212-523-7310 Fax 1: 212-523-8005 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17271.pdf Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of henle CONTACT: Andrew P. Evan Indiana University, School of Medicine Department of Anatomy and Cell Biology 635 Barnhill Drive MS 5055 Indianapolis, IN 46220 USA Phone 1: 317-274-7494 Fax 1: 317-278-2040 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17038.pdf ACCOMPANYING COMMENTARY: Nephrolithiasis: site of the initial solid phase CONTACT: David A. Bushinsky University of Rochester School of Medicine Chief, Nephrology Unit Strong Memorial Hospital 601 Elmwood Avenue, Box 675 Rochester, NY 14642 USA Phone 1: 585-275-3660 Fax 1: 585-442-9201 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18016.pdf Chronic myelogenous leukemia shapes host immunity by selective deletion of high avidity leukemia-specific T-cells CONTACT: Jeffrey J. Molldrem University of Texas M.D. Anderson Cancer Center Department of Blood and Marrow Transplantation Section of Transplantation Immunology 1515 Holcombe Boulevard, Box 448 Houston, TX 77030 USA Phone 1: 713-745-4820 Fax 1: 713-792-8312 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16398.pdf ACCOMPANYING COMMENTARY: Integrating the quality of the cytotoxic response and tumor susceptibility into the design of protective vaccines in tumor immunotherapy CONTACT: Salem Chouaib CJF 9411 INSERM Cytokines et Immunite Antilumorale INSITUT GUSTAVE ROUSSY 39, RUE DAMILLE DESMOULLNS Villejuif Cedex, 94805 FRANCE Phone 1: 33-1-4211-4547 Fax 1: 33-1-4211-5288 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18044.pdf Linkage of beta1-Adrenergic Stimulation to Apoptotic Heart Cell Death Through PKA-Independent Activation of Ca2+/Calmodulin Kinase II CONTACT: Rui-Ping Xiao Gerontology Research Center, NIA, NIH Laboratory of Cardiovascular Science 5600 Nathan Shock Drive Baltimore, MD 21224 USA Phone 1: 410-558-8662 Fax 1: 410-558-8150 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16326.pdf ACCOMPANYING COMMENTARY: Calcium and the heart: a question of life and death CONTACT: Andrew R. Marks Columbia University 630 W. 168th St. P & S Bldg. 9-401 New York, NY 10032 USA Phone 1: 212-305-0270 Fax 1: 212-305-3690 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18067.pdf FTY720 Stimulates Multidrug Transporter and Cysteinyl Leukotriene Dependent T Cell Chemotaxis to Lymph Nodes CONTACT: Jonathan Bromberg Mount Sinai School of Medicine One Gustave L. Levy Place Box 1104 New York, NY 10029-6574 USA Phone 1: 212-659-8008 Fax 1: 212-348-2474 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16200.pdf Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor CONTACT: Richard Breyer Vanderbilt University Division of Nephrology S3223 MCN 1161 21st Ave South Nashville, TN 37232-2372 USA Phone 1: 615-343-0257 Fax 1: 615-343-4704 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16492.pdf Liver-specific disruption of the peroxisome proliferator receptor gamma in diabetic mice improves fatty liver, but aggravates hyperglycemia CONTACT: Frank J. Gonzalez NIH, National Cancer Institute Laboratory of Metabolism Building 37, Room 3E-24 9000 Rockville Pike Bethesda, MD 20892 USA Phone 1: 301-496-9067 Fax 1: 301-496-8419 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17223.pdf Graft-versus-host disease (GVHD) can be separated from graft-versus-lymphoma effects by controlling lymphocyte trafficking with FTY720 CONTACT: Megan Sykes Massachusetts General Hospital Bone Marrow Transplantation Section, Transplantation Biology Research Center MGH East Building 149-5102 13th Street Boston, MA 02129 USA Phone 1: 617-726-4070 Fax 1: 617-724-9892 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16950.pdf c-Fms and the alphavbeta3 integrin collaborate during osteoclast differentiation
CONTACT: Steven L. Teitelbaum Washington Univ. School of Medicine Dept. of Pathology Barnes Jewish Hospital North, Mailstop 90-31-649 216 S. Kings Highway, Rm 2469 St. Louis, MO 63110 USA Phone 1: 314-454-8463 Fax 1: 314-454-5505 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16924.pdf |