Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


How to halt immune cell activation

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:

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

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>