JCI table of contents: June 22, 2009

Joel Drevet and colleagues, at Clermont Université, France, have identified a protein that helps protect immature mouse sperm after they have been released into a region of the testis known as the epididymis, which is where they undergo maturation. Although male mice lacking this protein, Gpx5, had normal looking sperm and were equally as efficient as normal male mice at fertilizing female mice, an increased incidence of miscarriages and fetal developmental defects were observed when normal female mice were mated with Gpx5-deficient males over 1 year old compared with normal male mice of the same age. Further analysis indicated that Gpx5 acts as an antioxidant in the epididymis, protecting the sperm from oxidative stress. As discussed by the authors, and, in an accompanying commentary, John Aitken, at the University of Newcastle, Australia, these data have immense clinical relevance as age-related DNA damage to human sperm has been associated with a range of adverse outcomes including decreased fertility, and increased rates of miscarriage and childhood disease.

TITLE: Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice

AUTHOR CONTACT:
Joel R. Drevet
CNRS UMR 6247, INSERM U931, Clermont Université, Aubière, France.
Phone: 33-4-73-40-74-13; Fax: 33-4-73-40-70-42; E-mail: joel.drevet@univ-bpclermont.fr.

View the PDF of this article at: https://www.the-jci.org/article.php?id=38940

ACCOMPANYING COMMENTARY
TITLE: Gpx5 protects the family jewels

AUTHOR CONTACT:
R. John Aitken
University of Newcastle, Newcastle, New South Wales, Australia.
Phone: 61-2-4921-2082; Fax: 61-2-4921-6308; E-mail: john.aitken@newcastle.edu.au.

View the PDF of this article at: https://www.the-jci.org/article.php?id=39688

In a recent phase II clinical trial, the drug alemtuzumab (Campath-1H) was found to be a highly effective treatment for individuals with early relapsing-remitting multiple sclerosis. However, a substantial proportion of the patients treated (30%) went on to develop another autoimmune disease, mostly thyroid autoimmunity. Now, Joanne Jones and colleagues, at the University of Cambridge, United Kingdom, have determined that individuals with higher levels of the soluble factor IL-21 in their blood prior to alemtuzumab treatment were those that went on to develop an autoimmune disease. Further analysis identified a mechanism by which IL-21 contributes to the development of autoimmunity and determined that in some patients the higher levels of IL-21 were genetically predetermined. The authors therefore suggest that measuring levels of IL-21 in the blood of individuals with early relapsing-remitting multiple sclerosis might identify those that would be at greatest risk of developing autoimmunity if treated with alemtuzumab. Terri Laufer and Gregory Wu, at the University of Pennsylvania, Philadelphia, further discuss the importance of this in an accompanying commentary, noting that determining one reason why some patients succumb to autoimmune disease after alemtuzumab treatment, while others do not, is likely to increase enthusiasm for this new therapeutic.

TITLE: IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H)

AUTHOR CONTACT:
Joanne L. Jones
University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Phone: 01223-216751; Fax: 01223-336941; E-mail: jls53@medschl.cam.ac.uk.

View the PDF of this article at: https://www.the-jci.org/article.php?id=37878

ACCOMPANYING COMMENTARY
TITLE: Treating MS: getting to know the two birds in the bush

AUTHOR CONTACT:
Terri M. Laufer
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-2955; Fax: (215) 573-7599; E-mail: tlaufer@mail.med.upenn.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=39963

Why the immune system of a pregnant woman does not attack her developing fetus is one of most remarkable features of pregnancy, and several underlying mechanisms have been described. However, Adrian Erlebacher and colleagues, at the New York University School of Medicine, New York, have now identified a new mechanism to explain why the mouse maternal immune system does not attack the fetuses.

Once an embryo implants into the wall of the uterus, a cellular structure known as the decidua forms around the embryo and placenta. In the study, the formation of the decidua was found to prevent immune sentinel cells known as DCs from leaving the maternal/fetal interface and traveling to the local lymph nodes to activate an immune response toward the fetus. The authors therefore suggest that impaired formation or function of the human decidua might allow DCs to leave the decidua to initiate an aggressive immune response toward the fetus, something that might contribute to poor pregnancy outcomes. In an accompanying commentary, Bali Pulendran, at Emory Vaccine Center at Yerkes National Primate Research Center, Atlanta, discusses how this new research affects current thinking about avoiding immune surveillance at the maternal/fetal interface.

TITLE: Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice

AUTHOR CONTACT:
Adrian Erlebacher
New York University School of Medicine, New York, New York, USA.
Phone: (212) 263-8926; Fax: (212) 263-8211; E-mail: adrian.erlebacher@nyumc.org.

View the PDF of this article at: https://www.the-jci.org/article.php?id=38714

ACCOMPANYING COMMENTARY
TITLE: Restraining order for dendritic cells: all quiet on the fetal front

AUTHOR CONTACT:
Bali Pulendran
Emory Vaccine Center at Yerkes National Primate Research Center, Atlanta, Georgia, USA.
Phone: (404) 727-8945; Fax: (404) 727-8199; E-mail: bpulend@emory.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=39946