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 More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>