When the immune system encounters a potential threat, antigen-presenting cells deliver chunks of protein from the invading pathogen to naive helper T cells.
These naive cells respond by differentiating into one of two classes of mature helper T cells: TH1 cells, which mobilize the immune system against viruses and other intracellular pathogens, and TH2 cells, which drive the response against blood-borne threats, such as the parasitic disease leishmaniasis.
Interleukin-4 (IL-4), one of a class of signalling factors known as cytokines, drives TH2 differentiation and triggers secretion of additional IL-4, resulting in a positive feedback loop that fuels TH2 production while suppressing TH1 production. The degree of initial IL-4 production varies considerably between individuals and the resulting ‘TH2 bias’ can have serious clinical implications. “TH2 bias is thought to be a mirror of allergic response, because many TH2 cytokines tightly associate with pathology of allergy,” says Masato Kubo, of the RIKEN Research Center for Allergy and Immunology in Yokohama.
TH2 bias also varies between different mouse strains, a fact that Kubo, Mark Bix of St. Jude’s Children’s Research Hospital in Memphis, USA, and colleagues exploited in a recent effort to identify determinants for this trait1. It was known that BALB/c strain mice have a high TH2 bias—producing large quantities of IL-4 following T cell activation—while B10.D2 mice have a 50-fold lower bias. However, a hybrid BALB/c strain generated by Kubo and Bix that contains a chunk of chromosome 16 from the B10.D2 strain also exhibited low bias, suggesting that this segment includes a gene pertinent to this characteristic.
Closer analysis spotlighted the Mina gene as a likely suspect; analysis of various mouse strains revealed that Mina gene activity and levels of Mina protein were inversely correlated with TH2 bias. Bix and Kubo’s team subsequently determined that Mina assembles into a larger multi-protein complex that directly binds to and inhibits the gene encoding IL-4, supporting a key role for this factor in TH2 bias.
The team’s analysis also identified nearly two dozen sequence variations in Mina that correlate with gene activity levels. These so-called single-nucleotide polymorphisms (SNPs) could provide useful diagnostic tools, and Kubo and Bix are now exploring this potential. “We have already done large-scale SNP analysis with Japanese and US populations,” says Kubo. “The human Mina locus has several SNPs, and some of them have weak correlation with atopic asthma in the Japanese population, but not in the US [population].”
The corresponding author for this highlight is based at the Laboratory for Signal Network, RIKEN Research Center for Allergy and Immunology
Do you have Feedback?
1. Okamoto, M., van Stry, M., Chung, L., Koyanagi, M., Sun, X., Suzuki, Y., Ohara, O., Kitamura, H., Hijikata, A., Kubo, M. & Bix, M. Mina, an IL4 repressor, controls T helper type 2 bias. Nature Immunology 10, 872–879 (2009).
Saeko Okada | Research asia research news
Further reports about: > Allergy > B10 > Bix > IL-4 > Immunology > Interleukin-4 > Leishmaniasis > RIKEN > SNP > T cells > TH1 > TH2 cells > Th2 > Tipping > allergic responses > diagnostic tool > diagnostic tools > gene activity > immune system > multi-protein complex > parasitic disease > single-nucleotide polymorphisms
Inactivate vaccines faster and more effectively using electron beams
23.03.2017 | Fraunhofer-Institut für Organische Elektronik, Elektronenstrahl- und Plasmatechnik FEP
Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung
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...
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...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
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...
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...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
22.03.2017 | Materials Sciences
22.03.2017 | Physics and Astronomy
22.03.2017 | Materials Sciences