Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research Reveals Inner Workings of Immune System ¡§Thermostat¡¨

22.08.2006
The immune system runs hot, sending out inflammatory infection-fighting proteins, then cools down by releasing anti-inflammatory soothers. A Brown University-led research team explains how this ¡§thermostat¡¨ works in the Journal of Immunology.

When bacteria, viruses or parasites attack, immune system cells unleash the soldiers. These ¡§hot¡¨ protein compounds kill invaders ¡V but also trigger inflammation, which, if unchecked, can destroy tissue, induce shock and kill the host. So immune system cells let loose another protein compound to cool down the immune response.

Precisely how this immune system ¡§thermostat¡¨ operates is unclear. The leading hypothesis is that these compounds ¡V which act as furnace and air conditioner ¡V battle it out over control of the system¡¦s inflammatory response.

But new research, led by George Yap of Brown University, shows that these cytokines don¡¦t operate independently and in opposition. They operate in harmony and are controlled by the same master. In work published in the Journal of Immunology, Yap and his team show that the ¡§cool¡¨ anti-inflammatory protein compound known as Interleukin 10 is activated by Interferon-£^, a class of proteins secreted by a class of white blood cells known as T helper 1 cells. The team then traced secretion of Interferon-£^ indirectly to tyrosine kinase 2, or tyk2, the same protein that signals ¡§hot¡¨ inflammatory cytokines Interleukin 12 and Interferon-£ and Interferon-£].

¡§Under the prevailing paradigm, scientists believe that the pro- and anti-inflammatory arms of the immune system just antagonize each other,¡¨ Yap said. ¡§Here we show that they actually induce each other. ¡¥Hot¡¦ cytokines don¡¦t inhibit ¡¥cool¡¦ ones ¡V they trigger their production. Wounding, in effect, triggers a healing process.¡¨

In previous research, Yap discovered that mutant mice with a naturally defective tyk2 gene were immune to arthritis, a condition caused by inflammation. But these mutants were much more susceptible to opportunistic infections. Why? Without tyk2, Yap found, mice didn¡¦t make enough of the pro-inflammatory warriors that destroy harmful bugs and cause inflammation. This finding established the notion that tyk2 signaling controlled Interleukin 12, the furnace side of the system. But what controlled Interleukin 10, the air conditioner?

To find out, Yap and his team conducted a series of experiments in mutant mice infected with the parasite Toxoplasma gondii. They found that Interleukin 10 production by T helper 1 cells is triggered by Interferon-£^ƒnƒ{ƒnbut not directly. Another cell, an antigen presenting cell or APC, sends a stimulatory signal back to the T helper 1 cell, ordering it to make Interleukin 10.

¡§What we see is that the ¡¥hot¡¦ and ¡¥cool¡¦ arms of the immune system aren¡¦t independently regulated,¡¨ Yap said. ¡§They talk to each other and respond in a dynamic and coordinated fashion.¡¨

Yap said the findings should send a message to drug companies designing and testing tyk2-inhibiting medicines for arthritis and other autoimmune diseases. Block tyk2 function, Yap said, and patients will be more prone to infection ¡V and their arthritis may not be relieved. ¡§There could be a downside to these drugs,¡¨ he said.

Brown graduate student Michael Shaw and Brown Medical School student Mark Scott contributed to the research. Gordon Freeman of the Dana-Farber Cancer Institute, Barbara Fox and David Bzik of Dartmouth Medical School and Yasmine Belkaid of the National Institute of Allergy and Infectious Disease served as collaborators.

The National Institute of Allergy and Infectious Diseases funded the research.

Wendy Lawton | EurekAlert!
Further information:
http://www.brown.edu

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>