Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inviting arthritic trouble

12.07.2010
A large-scale genetic screen reveals a factor that makes rheumatoid arthritis patients’ joints vulnerable to immune attack

Under normal conditions, the body is protected against immune system-mediated self-destruction by marker proteins that indicate that host cells are ‘off limits’ and should be ignored. In patients with rheumatoid arthritis (RA), however, such safeguards fail to prevent immune cells from damaging joint tissues.

Although an estimated 1% of the world’s population is affected by RA, the roots of this disorder are poorly understood. Now, a multi-institutional team of Japanese researchers led by Yuta Kochi and Kazuhiko Yamamoto of the RIKEN Center for Genomic Medicine in Yokohama has characterized potential genetic risk factors1.

The researchers performed a large-scale ‘genome-wide association study’, screening thousands of Japanese individuals to identify small genomic sequence variations—so-called ‘single-nucleotide polymorphisms’ (SNPs)—that are linked with RA susceptibility to a statistically meaningful degree. The strongest association they identified was for a SNP in the vicinity of the gene encoding chemokine (C-C motif) receptor 6 (CCR6). Subsequent analysis of two large, independent cohorts of Japanese subjects provided further confirmation of the connection between this CCR6 SNP and RA.

The CCR6 receptor recognizes signals that stimulate immune cell development, and triggers immune system effects that could be directly relevant to RA. “This receptor has been shown to be important for the migration and recruitment of immune cells such as dendritic cells, T cells, and B-cells during inflammatory and immunological responses” says Kochi, “and it may also regulate the differentiation and maturation of these cells.” Closer examination by the researchers subsequently revealed a second potentially important genetic variation affecting CCR6 expression. They also determined that the elevated CCR6 activity resulting from this variation was strongly associated with RA.

CCR6 appears to exert its pathological effects by promoting the inflammatory response triggered by a recently identified class of helper T cells known as Th17 cells. “We believe the primary role of CCR6 in RA pathogenesis is facilitating the entry of Th17 cells into the joints,” says Kochi. “And as CCR6 is also involved in the migration and differentiation of B-cells, it could also influence the activity of auto-reactive B-cells.” Strikingly, these CCR6 variants also appear to contribute to two other inflammatory conditions, Graves’ disease and Crohn’s disease.

Following on from this discovery, Kochi and Yamamoto are hopeful that their data will yield additional candidate genes that enable further insights into how RA patients’ immune systems end up going off-course. “Many other genetic factors other than CCR6 remain to be discovered,” says Kochi.

The corresponding author for this highlight is based at the Laboratory for Autoimmune Diseases, RIKEN Center for Genomic Medicine

Journal information

1. Kochi, Y., Okada, Y., Suzuki, A., Ikari, K., Terao, C., Takahashi, A., Yamazaki, K., Hosono, N., Myouzen, K., Tsunoda, T. et al. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nature Genetics 42, 515–519 (2010)

gro-pr | Research asia research news
Further information:
http://www.rikenresearch.riken.jp/eng/research/6330
http://www.researchsea.com

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>