Genetics: Identifying the CRAC in immunity; Gene therapy rescues immunodeficiency; Immune traffic express lane

Summaries of newsworthy papers from Nature Research Journals

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This press release contains:
* Summaries of newsworthy papers:
* Genetics: Identifying the CRAC in immunity - Nature
* Gene therapy rescues immunodeficiency - Nature Medicine
* Immune traffic express lane - Nature Immunology
* Mention of papers to be published at the same time with the same embargo
* Mention of a paper with an earlier embargo
* Geographical listing of authors

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[1] Genetics: Identifying the CRAC in immunity

A key protein involved in triggering the immune response against pathogens is described in a paper published online this week by Nature. The immune response relies on the movement of calcium ions through specific CRAC channels in T cells. However, CRAC channel function is defective in patients with hereditary severe combined immune deficiency (SCID) syndrome.

Anjana Rao and her colleagues set out to identify the underlying genetic defect in SCID patients using a combination of two unbiased genome-wide approaches: single-nucleotide polymorphism arrays and a Drosophila RNA interference screen. Both methods identified a protein called Orai1. The authors show that SCID patients are homozygous for a mutation in the gene encoding Orai1. When wild-type Orai1 is expressed in T cells from SCID patients, CRAC channel function is restored. The authors propose that Orai1 is either an essential regulator or a component of the CRAC channel
complex.

Author contact:
Anjana Rao (Harvard Medical School & CBR Institute for Biomedical Research, Boston, MA, USA)
Tel: +1 617 278 3260/3261; E-mail: [email protected]

********************NATURE MEDICINE**********
(<http://www.nature.com/naturemedicine>)

[2] Gene therapy rescues immunodeficiency

DOI: 10.1038/nm1393

A paper in the April issue of Nature Medicine reports clinical improvement on two adults who received gene therapy for the treatment of X-linked chronic granulomatous disease (X-CGD).
X-CGD is an immunodeficiency caused by a defect in the oxidative
antimicrobial activity of phagocytes -- a subpopulation of cells in the immune system. The disorder results from mutations in the gene gp91phox. The authors found substantial transfer of the gp91phox gene in both individuals, leading to a large number of functionally corrected phagocytes and notable clinical improvement.

Although the sites of the genome in which the gp91phox gene was inserted probably reinforced the therapeutic efficacy in this trial, these results suggest that gene therapy can be useful to treat X-CGD.

Author contact
Manuel Grez (Georg-Speyer-Haus, Gene Therapy Unit, Frankfurt, Germany)
Tel: +49 69 6339 5113; E-mail: [email protected]

Other papers from Nature Medicine to be published online at the same time and with the same embargo:

[3] Induction of leptin resistance through direct interaction of C-reactive protein with leptin
DOI: 10.1038/nm1372

[4] Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction
DOI: 10.1038/nm1391

[5] Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts
DOI: 10.1038/nm1394

****************NATURE IMMUNOLOGY*********************
(<http://www.nature.com/natureimmunology>)

[6] Immune traffic express lane

DOI: 10.1038/ni1319

A new traffic route for immune cells along the body's highways is presented in the May issue of Nature Immunology. Previously it was believed T cells, a type of immune cell, must circulate through specialized structures before migrating to pathogen-infected tissues.
Eugene Butcher and colleagues now demonstrate that some T cells bypass this normal trafficking route and instead can proceed directly to the intestine where the T cells become poised to battle any invading microbes.

Because the intestine is constantly exposed to pathogenic microbes, it requires rigorous patrolling by the immune system. Accordingly, over one billion T cells are found in the human small intestine. This direct freeway to the intestine may therefore ensure that this defense battalion is constantly replenished with fresh fighters able to take up arms against an array of pathogens.

Author contact:
Eugene C. Butcher (Stanford University School of Medicine, Stanford,
California USA)
Tel: +1 650 852 3369; E-mail: [email protected]

Other papers from Nature Immunology to be published online at the same time and with the same embargo:

[7] NKG2D-mediated signaling requires a DAP10-BOUND Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells DOI: 10.1038/ni1325

[8] A unique function for cyclin D3 in early B cell development
DOI: 10.1038/ni1324

Items from other Nature journals to be published online at the same time and with the same embargo:

NATURE MATERIALS (<http://www.nature.com/naturematerials>)

[9] Local density of states effects at the metal-molecule interfaces in a molecular device DOI: 10.1038/nmat1607

Nature CHEMICAL BIOLOGY (http://www.nature.com/nchembio
<http://www.nature.com/natureneuroscience>)

[10] Functional epitopes at the ribosome subunit interface
DOI: 10.1038/nchembio783

NATURE GENETICS (<http://www.nature.com/naturegenetics>)

[11] Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies
DOI: 10.1038/ng1770

[12] BBS10 encodes a vertebratespecific chaperonin-like protein and is a major BBS locus
DOI: 10.1038/ng1771

[13] MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion
DOI: 10.1038/ng1765

[14] Systematic identification of human mitochondrial disease genes through integrative genomics
DOI: 10.1038/ng1776

Nature NEUROSCIENCE <http://www.nature.com/natureneuroscience>)

[15] Activity-dependent regulation of inhibitory synaptic transmission in hippocampal neurons
DOI: 10.1038/nn1677

[16] Effects of visual experience on activity-dependent gene regulation in cortex
DOI: 10.1038/nn1674

[17] Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation
DOI: 10.1038/nn1678

[18] Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
DOI: 10.1038/nn1682

[19] Genetic mosaic with dual binary transcriptional systems in Drosophila DOI: 10.1038/nn1681

NATURE CELL BIOLOGY (<http://www.nature.com/naturecellbiology>)

[20] Individual dimers of the mitotic kinesin motor Eg5 step processively and support substantial loads in vitro
DOI: 10.1038/ncb1394

[21] The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-beta-catenin signalling through Dishevelled
DOI: 10.1038/ncb1405

[22] Chromatin signatures of pluripotent cell lines
DOI: 10.1038/ncb1403

[23] Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent and extension movements in Xenopus embryos DOI: 10.1038/ncb1399

NATURE IMMUNOLOGY

[24] Essential function in vivo for Dicer-2 in host defence against RNA
viruses in drosphila

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GEOGRAPHICAL LISTING OF AUTHORS

The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

BELGIUM
Leuven: 12

CANADA
Edmonton: 13
St John's: 11

CHILE
Santiago: 23

COLUMBIA
Medellin: 11

FINLAND
Helsinki: 11
Oulu: 11

FRANCE
Angers: 12
Bordeaux: 12
Lille: 12
Montpellier: 12
Vandoeuvre-les-Nancy: 12
Paris: 12, 13
Rennes: 12
Strasbourg: 12, 24

GERMANY
Bonn: 13
Erlangen: 5
Freiburg: 2
Frankfurt: 2
Hamburg: 5
Heidelburg: 2
Idar-Oberstein: 2
Leipzig: 5
Ulm: 9

GREECE
Athens: 22

ISRAEL
Bet-Dagan: 3

ISTANBUL
Turkey: 12

ITALY
Catanzaro: 13
Frieste: 13
Milan: 13, 14
Monza: 13
Naples: 13
Nuoro: 11
Parma: 13

JAPAN
Kanagawa: 4
Okoyama: 4
Osaka: 4
Saitama: 21
Tokyo: 4, 21

LUXEMBOURG
Luxembourg: 12

PORTUGAL
Braga: 11
Coimbra: 11, 12

SOUTH AFRICA
Pretoria: 11

SWEDEN
Stockholm: 2

SWITZERLAND
Basel: 9
Geneva: 18
Zurich: 2

THE NETHERLANDS
Amsterdam: 11
Rotterdam: 11, 12

THE UNITED KINGDOM
Bristol: 17
Cambridge: 10
Cardiff: 22
Harrow: 12
London: 2, 11, 12, 15, 22
Southampton: 11

THE UNITED STATES OF AMERICA

Alabama
Birmingham: 3
California
La Jolla: 24
Los Angeles: 11
Palo Alto: 6
San Diego: 11
Stanford: 6, 20, 1
Illinois
Chicago: 8, 1
Urbana: 19
Maryland
Baltimore: 12
Bethesda: 2, 6, 17
Frederick: 2
Massachusetts
Boston: 8, 14, 16, 1
Cambridge: 13, 14, 15, 1
Worcester: 19
Minnesota
Rochester: 7
Ohio
Cincinnati: 2
New York
New York: 11, 13
Texas
Houston: 12

PRESS CONTACTS...

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Beatrice Chrystall
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)
Orli Bahcall
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Published: 02 Apr 2006

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