JCI table of contents: January 12, 2006EDITOR'S PICK
Blockade of fat hormone helps halt and heal multiple sclerosis
Italian researchers have found that blockade of the hormone leptin, which is primarily produced in fats cells, has beneficial effects on the induction and progression of experimental autoimmune encephalomyelitis (EAE) in mice – the animal model of human multiple sclerosis (MS). In their study appearing online on January 12 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Giuseppe Matarese and colleagues from Università di Napoli "Federico II" suggest that leptin neutralization may be a potential way to both prevent and treat MS.
MS is an inflammatory disease of the brain and spinal chord characterized by muscle weakness, numbness, and loss of coordination. These symptoms result in part from destruction of the nerve-insulating material myelin by activated T cells.
Leptin is known to play a critical role in the regulation of food intake, metabolism, and the immune response. Since it had been previously shown that leptin is expressed in active inflammatory lesions of the central nervous system during EAE and MS, Matarese and colleagues investigated the effects of leptin blockade on the induction and progression of EAE in mice. They found that leptin blockade by the use of either anti-leptin antibodies or a form of the leptin receptor unable to bind leptin, either before or after disease onset improved clinical symptoms of disease, slowed disease progression, reduced disease relapses, and reduced the number of antigen-specific T cells. The authors delved further to unravel the cellular signaling events underlying these beneficial effects. Taken together, the data provide a basis for the development and testing of novel strategies of leptin-based targeting for the potential treatment of MS.
TITLE: Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis
Università di Napoli "Federico II", Napoli, Italy.
Phone: 39-081-7463311; Fax: 39-081-7463252; E-mail: [email protected]
View the PDF of this article at: https://www.the-jci.org/article.php?id=26523
Arthritis therapies may be able to bet on T-bet
In a study appearing online on January 12 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Laurie Glimcher and colleagues from the Harvard School of Public Health report an essential role for the protein T-bet in the development of inflammatory arthritis. This protein could provide an attractive new target for therapy for this painful and debilitating condition. Inflammatory arthritis can result when the body's immune system attacks its own healthy tissue and the protein T-bet is a critical regulator of the function of certain immune cells during this response. In their study, Glimcher et al. found that it is the expression of T-bet by dendritic cells, which once activated interact with T and B cells to initiate and shape the immune response, that is critical to the pathology of inflammatory arthritis. Mice lacking T-bet had markedly reduced joint inflammation and T-bet–deficient mice without T or B cells were essentially resistant to disease. They also found that transfer of normal dendritic cells that make T-bet, but not T-bet–deficient dendritic cells, into mice unable to make T cells, B cells or T-bet, was able to cause inflammatory arthritis. The study shows that the ability of dendritic cells to secrete proinflammatory molecules and to prime T cells to initiate an immune response is compromised in the absence of T-bet. T-bet could provide an attractive new target for therapy in inflammatory arthritis.
TITLE: Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells
Harvard School of Public Health
Phone: 617-432-0622; Fax: 617-432-0084; E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/article.php?id=26631
Insights from a mouse model of degenerative retinal disease are a sight for sore eyes
Choroideremia is a rare, inherited disorder found almost exclusively in males and is characterized by progressive loss of vision due to degeneration of the choroid and retina. The disorder is caused by a mutation in the CHM gene on the X chromosome, which codes for an important protein called the Rab escort protein-1 (REP-1), which shuttles other cellular proteins towards the cell membrane to allow the passage of nutrients in and out of the cell. The absence of REP-1 results in nutrient deficiency and degeneration of light-sensitive photoreceptors embedded within the thin layer at the rear of the eye (the retinal pigment epithelium, RPE), and the choroid (a layer filled with blood vessels that nourish the retina).
In a study appearing online on January 12 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Miguel Seabra and colleagues from Imperial College London report the development of the first mouse model of this degenerative eye disease. The authors go on to demonstrate that choroideremia involves independently triggered degeneration of photoreceptors and the RPE, and that these events are caused by different trafficking defects in various subsets of defective Rab proteins. This is an important finding as it was previously believed that RPE degeneration resulted in photoreceptor degeneration, and vice-versa. Development of an animal model for this disease will allow researchers to assess potential therapies and gain a better understanding of disease mechanisms.
TITLE: Independent generation of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia
Miguel C. Seabra
Imperial College London, London, United Kingdom
Phone: 44-20-7594-3024; Fax: 44-20-7594-3015; E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/article.php?id=26617
Type 3 deiodinase enzyme keeps thyroid hormones in check
Thyroid hormones (THs) are secreted by the thyroid gland and play a critical role in growth and development, so much so that reduced or excessive levels of THs during fetal and neonatal development can cause severe abnormalities. Type 3 deiodinase (D3) is involved in the degradation of thyroid hormones T3 and T4 to biologically inactive forms and as such serves as a modulator of intracellular TH levels and action. In order to learn more about the actions of D3, Arturo Hernandez and colleagues from Dartmouth Medical School examined mice deficient in the gene encoding D3 and observed marked abnormalities including early mortality, growth retardation, and impaired fertility. They found that in early life these mice had elevated T3 levels. Later, and into adulthood, the animals has low T3 and T4 levels characteristic of hypothyroidism (deficient thyroid activity). The study, which appears online on January 12 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, points to the importance of D3 in physiological processes such as growth, early development, and reproduction.
TITLE: Type 3 deiodinase is critical for the maturation and function of the thyroid axis
Dartmouth Medical School, Lebanon, New Hampshire, USA
Phone: 603-650-8078; Fax: 603-650-6130; E-mail: [email protected]
View the PDF of this article at: https://www.the-jci.org/article.php?id=26240
Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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