EDITOR'S PICK: Going bald without hair follicle progenitors
Androgenetic alopecia (AGA) is a frequent form of hair loss in both men and women. However, it is more common in men, in whom it is also known as male-pattern baldness. Through the analysis of bald and non-bald scalp samples from men with AGA, a team of researchers, led by George Cotsarelis, at the University of Pennsylvania School of Medicine, Philadelphia, has gained new insight into the underlying causes of AGA. Specifically, the data indicate that a defect in the conversion of hair follicle stem cells to progenitor cells has an important role in AGA. The authors therefore suggest that further studies defining the signals responsible for the transition of stem cells to progenitor cells could provide new therapeutic targets for the treatment of AGA.
TITLE: Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells
AUTHOR CONTACT:
George Cotsarelis
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: 215.898.9967; Fax: 215.573.9102; E-mail: cotsarel@mail.med.upenn.edu.
View this article at: http://www.jci.org/articles/view/44478?key=0a1481860c0b098075c7
EDITOR'S PICK: Dampening inflammation with aspirin
Inflammation is a protective response to invading microbes and tissue damage. Upon microbe clearance from the body or completion of wound healing, the inflammatory response must be dampened down. One set of molecules known to play a role in resolving the inflammatory response is the E-series resolvins. While analyzing the blood of several individuals to investigate the pathway by which E-series resolvins are generated, Charles Serhan and colleagues, at Harvard Medical School, Boston, identified a new 18S E-series resolvin. Importantly, the new resolvin reduced levels of pro-inflammatory molecules and cells in a mouse model of inflammation caused by the bacterium E. coli. Further, as the new resolvin could be generated from aspirin, the authors suggest that this molecule could contribute to the beneficial effects of aspirin.
TITLE: Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation
AUTHOR CONTACT:
Charles N. Serhan
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Phone: 617.525.5001; Fax: 617.525.5017; E-mail: cnserhan@zeus.bwh.harvard.edu.
View this article at: http://www.jci.org/articles/view/42545?key=4069526bb3558baf9ccf
VACCINE DESIGN: How to keep fungi at bay
Infections with fungi that initially start at one site (often the lung) and then spread to other organs in the body are known as systemic fungal infections. As rates of such infections have increased dramatically in recent years, researchers are keen on developing vaccines against these invasive microbes. A team of researchers, led by Marcel Wüthrich, at the University of Wisconsin, Madison, has now generated data in mice that provide insight into the type of immune response that such vaccines need to generate.
In North America, the three main fungi that cause systemic fungal infections are Coccidioides posadasii, Histoplasma capsulatum, and Blastomyces dermatitidis. In the study, immune cells known as Th17 cells were found to be sufficient for vaccine-induced protection against lethal lung infection with Blastomyces dermatitidis in mice. Further, vaccine-induced Th17 cells were necessary and sufficient to protect mice against all three of the fungi linked to the majority of cases of systemic fungal infection in North America. The authors therefore suggest that vaccines designed to prevent systemic fungal infections in humans should be designed to induce Th17 cells.
TITLE: Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice
AUTHOR CONTACT:
Marcel Wüthrich
University of Wisconsin, Madison, Wisconsin, USA.
Phone: 608.262.7703; Fax: 608.262.8418; E-mail: mwuethri@wisc.edu.
View this article at: http://www.jci.org/articles/view/43984?key=22b1a80a5663dc4420b2
IMMUNOLOGY: TRACking immune deficiency
Impaired functioning of the immune system can be an inherited condition. Mutations in any one of a large number of genes involved in immune cell function can cause such disorders. A team of researchers, led by Eammon Maher, at the University of Birmingham School of Medicine, United Kingdom, has now identified another gene that can be added to the list: TRAC. Individuals with mutations in this gene exhibited autoimmunity (a condition in which the immune system turns on cells and/or tissues of the patient's own body) and increased susceptibility to certain infections. However, they surprisingly were protected from many infections, indicting that the TRAC mutations lead to only a partial immunodeficiency.
TITLE: Mutation in the TCR-alpha subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCR-alpha-beta+ T cells
AUTHOR CONTACT:
Eamonn R. Maher
University of Birmingham School of Medicine, Birmingham, United Kingdom.
Phone: 44.121.627.2741; Fax: 44.121.414.2538; E-mail: e.r.maher@bham.ac.uk.
View this article at: http://www.jci.org/articles/view/41931?key=298a95f51658bfbedd1b
INFLAMMATION: New point of control for inflammation: the soluble factor leukotriene B4
Inappropriate inflammation is central to many diseases, including asthma, autoimmune disease, and atherosclerosis (often known as hardening of the arteries). Signaling through several sets of cell surface molecules on immune cells known as macrophages is a key driver of inflammation. In particular, signaling through proteins that rely on the adaptor protein MyD88. A team of researchers, led by Marc Peters-Golden and Carlos Serezani, at the University of Michigan Health System, Ann Arbor, has now shown that mouse macrophage inflammatory responses dependent on MyD88 are reduced in the absence of signals triggered by the molecule leukotriene B4 (LTB4). These data have clinical importance, as they suggest that inhibitors of LTB4 generation and or antagonists of the molecule to which it binds might provide a new therapeutic approach to dampening inflammatory disease.
TITLE: Leukotriene B4 amplifies NF-kappa-B activation in mouse macrophages by reducing SOCS1 inhibition of MyD88 expression
AUTHOR CONTACT:
Marc Peters-Golden
University of Michigan Health System, Ann Arbor, Michigan, USA.
Phone: 734.763.9077; Fax: 734.764.4556; E-mail: petersm@umich.edu.
Carlos H. Serezani
University of Michigan Health System, Ann Arbor, Michigan, USA.
Phone: 734.615.5523; Fax: 734.764.4556; E-mail: cserezan@med.umich.edu.
View this article at: http://www.jci.org/articles/view/43302?key=122f690f1a4619d60b0d
NEUROBIOLOGY: New link between distinct neurological diseases
Amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease) and frontotemporal lobar degeneration (FTLD) are clinically quite distinct, although a few patients have some overlapping symptoms. However, both conditions are characterized by aggregates that contain the protein TDP-43 in the cytoplasm (the jelly-like substance that fills the cell) of nerve cells in the brain and spinal cord. Surprisingly, Virginia Lee and colleagues, at the University of Pennsylvania School of Medicine, Philadelphia, have now determined, using mice expressing either normal human TDP-43 or a mutant form of human TDP-43 that localized to the cytoplasm rather than the nucleus (the normal location for the protein), that the presence of TDP-43 cytoplasmic aggregates do not correlate with nerve cell death. Rather, nerve cell death correlated with loss of mouse TDP-43 in the nucleus, which led to profound alterations in gene expression. These data provide new insight into the link between TDP-43 and neurological disease.
TITLE: Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice
AUTHOR CONTACT:
Virginia M.-Y. Lee
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: 215.662.6427; Fax: 215.349.5909; E-mail: vmylee@mail.med.upenn.edu.
View this article at: http://www.jci.org/articles/view/44867?key=5fcbdccd59ebc8a3542e
VIROLOGY: The protein A20 an impediment to HIV immunity
Preventing and/or containing HIV transmission requires immune responses throughout the body (i.e., systemic immune responses) and at the site of infection (i.e., mucosal surfaces such as the lining of the vagina). Ideal HIV vaccines should activate both of these immune responses, but approaches currently under development rarely do. A team of researchers, led by Si-Yi Chen and Xue Huang, has now found that downregulating expression of the protein A20 on immune cells known as DCs enhances their ability to induce both mucosal and systemic immune responses to HIV proteins in mice. The authors suggest that although further preclinical studies are necessary, these data might help researchers develop an efficient HIV vaccination strategy.
TITLE: Mucosal and systemic anti-HIV immunity controlled by A20 in mouse dendritic cells
AUTHOR CONTACT:
Si-Yi Chen
University of Southern California, Los Angeles, California, USA.
Phone: 323.442.7727; Fax: 323.442.7729; E-mail: siyichen@usc.edu
Xue F. Huang
University of Southern California, Los Angeles, California, USA.
Phone: 323.442.7727; Fax: 323.442.7729; E-mail: xuefhuan@usc.edu.
View this article at: http://www.jci.org/articles/view/42656?key=ee478abd222bbf3fdcc3
Journal
Journal of Clinical Investigation