Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How to halt immune cell activation

13.10.2008
Researchers in Japan have identified part of the mechanism responsible for preventing prolonged—and potentially dangerous—activation of immune cells called T lymphocytes .

A new study sheds light on the molecular machinery required for reining in cellular signals that, if unleashed, could result in pathological inflammation

Researchers in Japan have identified part of the mechanism responsible for preventing prolonged—and potentially dangerous—activation of immune cells called T lymphocytes (1). Each decorated with a unique surface receptor (TCR) capable of detecting pathogenic foreign proteins, T lymphocytes circulate throughout the body patrolling for invading microorganisms. Upon encounter with rogue proteins, TCRs trigger—via a complex of CD3 signaling proteins—intracellular events that orchestrate release of pro-inflammatory mediators called cytokines.

As unrestrained inflammation can cause tissue damage, the immune system exerts tight control over T lymphocyte activation. During healthy conditions, TCR and CD3 proteins are constantly internalized and released back to the lymphocyte surface; this ‘recycling’ maintains a low level of TCR expression and thus a high ‘threshold’ precluding unwarranted activation. After stimulation, however, TCRs and CD3 subunits are routed towards destructive intracellular compartments called lysosomes, where they are degraded as part of a signal ‘shut off’ mechanism.

A team led by Ji-Yang Wang of the RIKEN Center for Allergy and Immunology in Yokohama sought to identify proteins underpinning this ‘fail safe’ TCR signal termination process.

Having noted in previous experiments that expression of the lysosomal protein LAPTM5 is altered after TCR stimulation, the researchers tested whether LAPTM5 is involved in turning off TCR signals. They used genetic manipulation techniques to generate mutant mice in which the Laptm5 gene is not expressed. These Laptm5-deficient animals exhibited excessive T lymphocyte-driven responses to skin sensitization.

The team also found that, compared to normal T lymphocytes, LAPTM5-deficient T lymphocytes underwent more cell divisions, and released the cytokines interferon-ã and interleukin-2 more frequently after TCR stimulation. After activation, T lymphocytes lacking LAPTM5 expressed higher amounts of surface and intracellular TCR and a CD3 subunit, CD3æ, than did wild-type T lymphocytes. Conversely, overexpression of LAPTM5 dampened CD3æ expression.

TCR and CD3æ proteins co-localized with LAPTM5 in lysosomes of activated T cells, and LAPTM5 physically interacted with CD3æ (Fig. 1). These findings indicate that LAPTM5 might promote CD3æ degradation by binding to and shuttling this protein to lysosomes.

Whether LAPTM5 cooperates with other lysosomal proteins to orchestrate CD3æ destruction, and whether any human immune disorders are associated with mutations in Laptm5, remains to be determined.

LAPTM5 is the first lysosomal protein known to be specifically expressed in blood-generating (hematopoietic) cells. “In addition to its role in the negative regulation of TCR signaling, preliminary studies indicate that LAPTM5 may regulate the cell surface expression of additional immune receptors and may also function to prevent hematopoietic malignancies,” says Wang.

1. Ouchida, R., Yamasaki, S., Hikida, M., Masuda, K., Kawamura, K., Wada, A., Mochizuki, S., Tagawa, M., Sakamoto, A., Hatano, M., Tokuhisa, T., Koseki, H., Saito, T., Kurosaki, T. & Wang, J.Y. A lysosomal protein negatively regulates surface T cell antigen receptor expression by promoting CD3æ-chain degradation. Immunity 29, 33–43 (2008).

Saeko Okada | ResearchSEA
Further information:
http://www.rikenresearch.riken.jp/research/558/
http://www.researchsea.com

Further reports about: CD3 CD3æ LAPTM5 T lymphocytes TCR TCRs trigger activation cell activation immune cell lymphocyte lysosomal

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>