ONLINE 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: boitard@cochin.inserm.fr
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: alichtman@rics.bwh.harvard.edu
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: douglas.losordo@tufts.edu
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: chendong@u.washington.edu
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: j.c.leemans@amc.uva.nl
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: jb39@columbia.edu
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: evan@anatomy.iupui.edu
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: david_bushinsky@urmc.rochester.edu
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: jmolldre@notes.mdacc.tmc.edu
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: chouaib@igr.fr
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: Xiaor@GRC.NIA.NIH.GOV
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: arm42@columbia.edu
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: jon.bromberg@mountsinai.org
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: rich.breyer@vanderbilt.edu
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: fjgonz@helix.nih.gov
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: megan.sykes@tbrc.mgh.harvard.edu
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: teitelbs@medicine.wustl.edu
View the PDF of this article at: https://www.the-jci.org/press/16924.pdf
Journal
Journal of Clinical Investigation