Wednesday , December 1 2021

The "Happy Hormone" building block activates the immune cells



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IMBA researchers, along with the Boston Children's Hospital in Harvard, showed a whole new way of combating autoimmune diseases and cancer.

Vienna (OTS) For decades, researchers have tried to discover the various mechanisms of our immune system. Observation methods observed over the last decade have paved the way for a new era of cancer treatment. If the immune system itself can be activated, the body can defend itself against cancer cells and other invaders. This approach to revolutionizing cancer treatment was this year's Nobel prize for medicine. Now an international team of researchers led by Josef Penninger from the Institute of Molecular Biotechnology in Vienna (IMBA) and Clifford Woolf from Harvard's Boston Children's Hospital is leading a completely new understanding of immunology cell biology, which is widely applied in medicine.

Immune Response Key Player

Amazing thing: our body's immune cells, called T-cells, activate a molecule that plays an important role in metabolism in our nervous system. To date, tetrahydrobiopterin or BH4 was known to be necessary for the production of currants, such as the "happiness hormone" for serotonin and dopamine. It's exciting for our discoveries that a system that is really known in neurobiology can play such an important role in T cell immune defense, "says Josef Penninger, IMBA founder and author of the current publication in the journal. nature"This new approach binds two totally different systems to our body and is different from all known immune control sites. In addition, treatment options are extensive: from autoimmune diseases, asthma and cancer allergy!"

BH4 is involved in many metabolic processes in our body. Since the 80's, it has also been known that people with iron deficiency or anemia often suffer from immune problems, but this relationship could not be explained. Now we know why: BH4 controls the growth of the T cell, "our immune system soldier," by regulating iron metabolism and mitochondrial activity, cell "power stations".

T cells patrol our bodies and emit pathogens or degenerate cells that may become tumors. In such cases, T cells are activated, multiplied, and attacked by a kind of attack to target invaders or target cancer cells. Often the problem: the wrong activated T cells are directed against the body's cells – this happens, for example, in allergic reactions and autoimmune diseases such as colitis, asthma, multiple sclerosis, arthritis, or certain skin diseases.

Hattrick: Clinical use against autoimmune diseases, allergies and cancer

"Autoimmune diseases and allergies are one of the most common diseases in the world, and therapy is urgently needed. Here, our discovery can be extremely useful, and inhibition of BH4 inhibits this type of continuous T-cellular attack, preventing the destruction of healthy tissues or causing chronic inflammation," said Shane Cronin, imbalanced by a postgraduate researcher and current publications by Nature's first author. Researchers at the Boston Children's Hospital Clifford Woolf and Harvard and Kai Johnsson, Max Planck Medical Research Institute in Heidelberg, developed a new drug called QM385 that inhibits BH4 and immune cells "suppress violent excessive reactions". The first clinical trials are done.

BH4 is also a significant candidate for future cancer immunotherapy, since activated T cells experience and fight cancer cells. Researchers now found in mice that BH4 helps T-cells target target tumors. In addition, it has been shown that BH4 is blocked by kinurenin, a molecule that can be excluded in immune tumors. Administration of BH4 causes T cells to grow again.

"Knowledge of new biology relationships and the emergence of illnesses are particularly valuable as applications can be very diverse. Who would have thought that our immune system could be controlled by a molecule known to be neurobiologically and possibly lead to new uses against autoimmune diseases, asthma , cancer and immune deficiency? "says Shane Cronin.
"If you can find interconnections between different body biological systems, such as the nervous system and the immune system in this case, sometimes you can create striking discoveries." In the past, the Josef Penninger team, for example, using the RANKL signaling path, managed to link bone metabolism and the hormonal system. The medicine derived from the treatment, Denosumab, is from bone loss to breast cancer pills currently tested in Austria.

Initial publication: "Metabolite BH4 Controls T Cell Proliferation in Autoimmunity and Cancer", Cronin et al. Nature, 2018, DOI: 10.1038 / s41586-018-0701-2

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About IMBA

IMBA – Molecular Biotechnology Institute is one of the leading biomedical research institutes in Europe. The main focus is on medical issues in the field of stem cell biology, RNA biology, molecular disease models and genetics. The Institute is based in Vienna's BioCenter, a dynamic conglomerate of universities, academics and biotechnology companies. IMBA is the Austrian Academy of Sciences, the leading non-university research body in Austria. www.imba.oeaw.ac.at

Requests and contact information:

Mag. Inese Miu-Blantara
Senior Communications Manager
IMBA – Molecular Biotechnology Institute GmbH
Dr. Bohr-Gasse 3, 1030 in Vienna
M: +43 664 808473828
E: ines.mehu-blantar@imba.oeaw.ac.at
www.imba.oeaw.ac.at

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