Preventing an immune over-reaction
The immune system can run awry in many ways. Some examples of undesirable immune responses include those directed against the host (autoimmunity), transplanted organs (transplant rejection), or a harmless substance (allergies). In each case, the immune system is reacting to the presence of a molecule known as an antigen. Currently, the best treatment options involve broad spectrum suppression of the immune system, which increases susceptibility to infection. A preferable solution would be to specifically turn off the immune cells that respond to non-threatening objects. In this issue of the Journal of Clinical Investigation, Dr. James Paulson and colleagues at The Scripps Research Institute in La Jolla, California used antigen-decorated nanoparticles to block the development of antibodies to a immune response-inducing antigens in mice. In an accompanying commentary, Edward Clark of the University of Washington discusses how this finding could lead to therapeutic agents capable of precisely controlling our immune system, allowing favorable responses and inhibiting unfavorable responses.
TITLE: Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis
AUTHOR CONTACT:
James C Paulson
The Scripps Research Institute, La Jolla, CA, USA
Phone: 858-784-9634; Fax: 858-784-9690; E-mail: jpaulson@scripps.edu
View this article at: http://www.jci.org/articles/view/69187?key=d3ac5675f0e4224288c1
ACCOMPANYING COMMENTARY
TITLE: STALing B cell responses with CD22
AUTHOR CONTACT:
Edward A Clark
University of Washington, Seattle, WA, USA
Phone: 206 543-8706; E-mail: Eclark@wanprc.org
View this article at: http://www.jci.org/articles/view/69670?key=0b5f09cda9a91d9896b6
A potential gene therapy for Mucopolysaccharidosis Type IIIA
Mucopolysaccharidosis Type IIIA (MPSIIIA) is a metabolic disorder in which the body is missing an enzyme that is required to break down long chains of sugars known as glycosaminoglycans. Over time, the glycosaminoglycans collect in the body and cause damage, particularly in the brain. In this issue of the Journal of Clinical Investigation, Fàtima Bosch and colleagues at Universitat Autònoma de Barcelona in Spain developed a form of gene therapy to replace the enzyme that is missing in MPSIIIA. By injecting the replacement gene into the the cerebrospinal fluid that surrounds the brain and spinal cord, Bosch and colleagues found that they could successfully deliver a replacement gene to the brain in mice and dogs. This study demonstrates that gene therapy can be delivered to the brain through the cerebrospinal fluid and suggests that this approach could potentially be used as a therapy for MPSIIIA.
TITLE: Whole body correction of Mucopolysaccharidosis IIIA by intra-cerebrospinal fluid gene therapy
AUTHOR CONTACT:
Fàtima Bosch
Universitat Autònoma de Barcelona, Bellaterra, UNK, ESP
Phone: 0034935814182; Fax: 0034935814180; E-mail: fatima.bosch@uab.es
View this article at: http://www.jci.org/articles/view/66778?key=d24b37bc3364f9761834
A new target in castration-resistant prostate cancer
The prostate gland requires male hormones, known as androgens, in order to function. Androgens act through cell surface receptors (androgen receptors) that initiate changes in prostate cells. In prostate cancer, androgens promote the growth and spread of cancer cells; consequently, therapeutics that block androgen receptors are effective in many prostate cancer patients. Unfortunately, the disease frequently recurs in a lethal, androgen-independent form (CRPC) that is associated with mutations in androgen receptors. In this issue of the Journal of Clinical Investigation, Marianne Sadar and colleagues at the BC Cancer Agency in Vancouver, British Columbia, investigated a drug, EPI-001, which blocks the activity of the mutant androgen receptors through interaction with a region of the receptor known as the N-terminal domain. Using a mouse model of prostate cancer, Sadar and colleagues found that EPI-001 reduced the growth of prostate cancer. These findings suggest that drugs similar to EPI-001 could potentially be used to treat androgen-independent forms of prostate cancer.
TITLE: An androgen receptor N-terminal domain antagonist for treating prostate cancer
AUTHOR CONTACT:
Marianne Sadar
BC CANCER AGENCY, VANCOUVER, BC, CAN
Phone: 604 675 8157; E-mail: msadar@bcgsc.ca
View this article at: http://www.jci.org/articles/view/66398?key=b9daf88e2e1a4c7dfa50
ALSO IN THIS ISSUE
TITLE: Immune cells control skin lymphatic electrolyte homeostasis and blood pressure
AUTHOR CONTACT:
Jens Titze
Vanderbilt University Medical Center, Erlangen, DEU
Phone: +1 615 8009458; E-mail: jens.m.titze@vanderbilt.edu
View this article at: http://www.jci.org/articles/view/60113?key=927cad5d868db1fc7de5
TITLE: 11β-hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects
AUTHOR CONTACT:
Ana Tiganescu
UCSF-NCIRE, San Francisco, CA, USA
Phone: +1 415-750-6954; E-mail: ana.tiganescu@ncire.org
View this article at: http://www.jci.org/articles/view/64162?key=dc085d4622b4d3c6c54a
TITLE: Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis
AUTHOR CONTACT:
Shyam Biswal
Johns Hopkins University, Baltimore, MD, USA
Phone: 410-955-4728; E-mail: sbiswal@jhsph.edu
View this article at: http://www.jci.org/articles/view/66353?key=92077a338c57eb874662
TITLE: Dominant protein interactions that influence the pathogenesis of conformational diseases
AUTHOR CONTACT:
Peter Arvan
University of Michigan Medical School, Ann Arbor, MI, USA
Phone: 734 936-5505; Fax: 734 936-6684; E-mail: parvan@umich.edu
View this article at: http://www.jci.org/articles/view/67260?key=7a6c724c37397f2c5343
TITLE: PRKDC mutations in a SCID patient with profound neurological abnormalities
AUTHOR CONTACT:
PA Jeggo
GDSC University of Sussex, Sussex, GBR
Phone: 00441273678482; Fax: 00441273678121; E-mail: p.a.jeggo@sussex.ac.uk
View this article at: http://www.jci.org/articles/view/67349?key=951c51809f3c321f2247
TITLE: Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus
AUTHOR CONTACT:
Mariana Kaplan
University of Michigan, Ann Arbor, MI, USA
Phone: 734-763-3031; Fax: 734-763-4151; E-mail: makaplan@umich.edu
View this article at: http://www.jci.org/articles/view/67390?key=74450c3b6d9bf942d817
Journal
Journal of Clinical Investigation