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JCI online early table of contents: Aug. 3, 2009

JCI Journals

EDITOR'S PICK: Maternal immunity not all good for a fetus

As a fetus does not mount an immune response to maternal proteins that cross the placenta, it has been assumed that a fetus would not reject non-genetically matched blood cells (specifically allogeneic blood cells) if they were transplanted while the fetus was in utero. The hope is that this procedure, which is known as IUHCT, could provide a viable approach for treating congenital blood disorders. However, studies using a mouse model of IUHCT indicate that most fetal recipients of allogeneic blood cells lose their transplanted cells 3-5 weeks after transplantation. Alan Flake and colleagues, at Children's Hospital of Philadelphia, have now identified an immune mechanism responsible for graft failure in this model of IUHCT. Surprisingly, although fetal immune cells eliminated the transplanted allogeneic blood cells, they were triggered to do so by immune molecules known as alloantibodies that they obtained from their mother's breast milk. The maternal alloantibodies were produced in response to IUHCT and so the authors conclude that in the absence of either a maternal immune response or transmission of the maternal alloantibodies to the fetus, transplanted blood cells should not be rejected, leaving open the door for IUHCT as a potential clinical strategy.

TITLE: Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in mice

AUTHOR CONTACT:
Alan W. Flake
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Phone: (215) 590-3671; Fax: (215) 590-3324; E-mail: flake@email.chop.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=38979


EDITOR'S PICK: 'SIRT'ain security: the protein SIRT3 protects the heart

Sirtuin proteins have been shown to promote longevity in many organisms, and increased expression of one sirtuin protein, SIRT3, has been linked to increased human lifespan. New data, generated in mice, by Mahesh Gupta and colleagues, at the University of Chicago, Chicago, has revealed that Sirt3 helps protect the mouse heart.

In the study, the heart of mice lacking Sirt3 was found to show signs of becoming enlarged (a process known as cardiac hypertrophy), at about 8 weeks of age. Further, these mice responded dramatically to conditions that induce cardiac hypertrophy, whereas mice overexpressing Sirt3 were protected from cardiac hypertrophy under the same conditions. Additional analysis revealed the mechanism by which Sirt3 blocks the cardiac hypertrophic response, thereby providing protection to the mouse heart. Specifically, it acts in heart muscle cells via the protein Foxo3a to increase expression of anti-oxidant proteins, thereby reducing levels of damaging oxidants.

TITLE: Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice

AUTHOR CONTACT:
Mahesh P. Gupta
University of Chicago, Chicago, Illinois, USA.
Phone: (773) 834-7811; Fax: (773) 834-9114; E-mail: mgupta@surgery.bsd.uchicago.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=39162


EDITOR'S PICK: The protein CCKR2: a potential drug target for colorectal cancer?

Colorectal cancer, the second most common cause of death from cancer in the United States, is associated with an abnormally high rate of increase in the number of cells lining the colon (colonic hyperproliferation). In mice, overexpression of the human protein progastrin has been shown to cause colonic hyperproliferation and promote colorectal cancer, but the molecular mechanisms underlying this have remained undetermined. In a new study, Timothy Wang and colleagues, at Columbia University Medical Center, New York, have revealed a key link between the protein CCKR2 and progastrin-related colonic hyperproliferation. Initial analysis indicated that the Cck2r gene was upregulated in mice that overexpressed human progastrin. Deletion of this gene in mice that overexpressed human progastrin abolished the colonic hyperproliferation induced by the high levels of human progastrin and markedly diminished the extent of experimentally induced colorectal cancer. As previously published data indicate that levels of progastrin might be elevated in individuals with colorectal cancer, the authors conclude that their study suggests that CCKR2 may be a viable target for the development of drugs to treat or prevent colorectal cancer.

TITLE: Inactivating cholecystokinin-2 receptor inhibits progastrin-dependent colonic crypt fission, proliferation, and colorectal cancer in mice

AUTHOR CONTACT:
Timothy C. Wang
Columbia University Medical Center, New York, New York, USA
Phone: (212) 851-4581; Fax: (212) 851-4590; E-mail: tcw21@columbia.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=38918


PULMONARY BIOLOGY: Blood clotting protein linked to scarring in the lung

TITLE: Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury

AUTHOR CONTACT:
Rachel C. Chambers
University College London, London, United Kingdom.
Phone: 44-207679-6978; Fax: 44-207679-6973; E-mail: r.chambers@ucl.ac.uk.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33288


DERMATOLOGY: Cells known as pericytes help regenerate skin tissue

TITLE: A role for pericytes as microenvironmental regulators of human skin tissue regeneration

AUTHOR CONTACT:
Pritinder Kaur
Peter MacCallum Cancer Centre, St Andrew's Place, Melbourne, Victoria, Australia.
Phone: 61-3-9656-3714; Fax: 61-3-9656-1411; E-mail: pritinder.kaur@petermac.org.

View the PDF of this article at: https://www.the-jci.org/article.php?id=38535


TUMOR IMMUNOLOGY: Time is of the essence: how rapidly different T cell types respond determines whether or not a tumor is destroyed

TITLE: Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice

AUTHOR CONTACT:
David Klatzmann
Hôpital Pitié-Salpêtrière, Paris, France.
Phone: 33-1-42-17-74-61; Fax: 33-1-42-17-74-62; E-mail: david.klatzmann@upmc.fr.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36628

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