Research findings may pave way for innovative treatments of multiple sclerosis

Inhibition of the protein kinase CK2 prevents the development of auto-aggressive T cells

Researchers at the Research Center for Immunotherapy (FZI) and the Focus Program Translational Neurosciences (FTN) of Johannes Gutenberg University Mainz (JGU) have identified a new mechanism that is involved in the development of autoimmune diseases. On the basis of this new insight, it may prove possible to create innovative treatments for disorders such as multiple sclerosis (MS). The members of the research team headed by Professor Tobias Bopp at the Institute of Immunology at the Mainz University Medical Center and Professor Frauke Zipp at the Department of Neurology, were able to demonstrate that it is possible to influence the development and functioning of regulatory T cells, also known as Tregs, and T helper 17 (TH17) cells by means of inhibition of the protein kinase CK2. It would seem that many of the devastating effects of autoimmune disorders are attributable to TH17 cells. Among other factors, the relative levels of these two types of cells determine whether or not an autoimmune disorder develops. For this reason, the researchers aimed to create an imbalance in favor of the Tregs. They were able to achieve this by inhibiting the development of the auto-aggressive TH17 cells through a blockade of CK2 and the simultaneous promotion of the synthesis of Tregs. The efficacy of this approach has already been impressively confirmed in pre-clinical models. The results of the Mainz study "Protein kinase CK2 governs the molecular decision between encephalitogenic TH17 cell and Treg cell development" are available in the online version of the leading specialist journal Proceedings of the National Academy of Sciences (PNAS).

The human immune system is extremely efficient in recognizing intruders that could be potentially damaging to health. A sub-group of white blood cells, the so-called T cells, identify invading pathogens on the basis of their proteins and normally orchestrate an appropriate qualitative and quantitative defensive immune reaction. This neutralizes the exogenous invaders in a targeted manner and eliminates them. In rare cases, this type of defensive reaction may culminate in an exaggerated immune response. It is to prevent exactly such excessive immune reactions that regulatory T-cells, the so-called Tregs, have evolved over time.

In healthy individuals, these Tregs serve to maintain immunological tolerance. They protect harmless antigens such as foreign proteins in food that might otherwise trigger an endogenous defensive reaction, as well as the body's own structures in the case of inappropriately activated immune responses. They thus also prevent the development of allergies and autoimmune disorders, including multiple sclerosis (MS).

A sub-population of T helper cells, the so called Interleukin-(IL)17 producing TH17 cells, plays a major role in the development of MS. In healthy individuals, these TH17 cells are responsible for the control of infecting bacteria and fungi. However, TH17 cells also have a potentially negative, auto-aggressive effect in that they can be responsible for the destructive processes that occur in the presence of inflammations and also in many autoimmune conditions.

The researchers at the Mainz University Medical Center now discovered that not only the ratio of Tregs to TH17 cells decisively determines whether or not an autoimmune disorder develops but also, and more importantly, that pharmacological inhibition of CK2 tips the balance of the two cell types towards Tregs.

Protein kinases are the second largest family of proteins present in higher cells. They modify other proteins and thus change the biological properties of these proteins. The researchers were able to show that inhibition of the protein kinase CK2 results in a blockade of exactly those signal pathways required by TH17 cells in order to evolve. On a molecular level, the inhibition of the protein kinase CK2 leads to inhibition of the signal pathways mediated by the cytokines interleukin-6, interleukin-21, and interleukin-23 as well as those that regulate gene expression through the transcription factor STAT3. This leads to the expression of another transcription factor called forkhead-box protein P3 (FOXP3), which in its turn controls the development and functioning of Tregs by means of genetic regulation. Thus, the auto-aggressive TH17 cells that are actually involved in the generation of autoimmune diseases are 'deprogrammed' in cells which protect endogenous structures, hence preventing the onset of these disorders.

Source: Universität Mainz

Comments

  1. Wendy Allen Wendy Allen United States says:

    Awesome research! This may even help Celiac/gluten issues which may affect 90% of the population. To me MS is due to Celiac which hurts the gut lining so less nutrients absorb...then cells are not made right to work right to burn oxygen. Low oxygen in my brain causes my MS.  Gluten may affect the thyroid (lowering oxygen)/adrenals (stealing progesterone) and other glands.  Gluten may lower the immune system so infections like Lyme/Epstein Barr may  happen. Ozone/herbs/Far Infrared Sauna etc. may help infections. Zyto scans show organ/infections etc. Hair tests show good minerals/heavy metals. Taking vitamins/good oils/minerals/probiotic/zinc/Mg/biotin 5000mcg/fish oil 2000mg/evening primrose oil 2000mg/lecithin 2000mg/Vit C/rhodiola/coenzyme Q10/Vit B12 methylcobalamin shot/intrinsic factor kind (helps raise oxygen and remyelinate the brain/helps the bones)/MTHF folate/Nature's plus- Source of life multiple/HCl and enzymes with meals  help my MS. LDN/gluten enzymes help block hidden gluten. Gluten is wheat/barley/rye/oats/corn/rice. Microscopic gluten hurts me.
             Bioidentical hormones..estriol/progesterone/testosterone which helps circulation/thyroid/immune system/blood sugar/blood pressure etc.... and EDTA/DMPS IV chelations that unclog my blood vessels and remove heavy metals help me. Th1/Th2 foods may affect swelling. Th2 foods right now swell me. I currently have Lyme...30 years after getting MS due to Celiac.  Celiac may affect the liver so it doesn't detox well and heavy metals may build up that block the thyroid and other chemical reaction. Celiac is due to low sunlight heritage or people new to eating these foods. 5000IU of Vit D3/sunlight/exercise/good water/organic vegetables/low sugar fruit and more may help. Gluten/dairy/soy/sugar/GMO/heated oils/saturated fat/monounsaturated fat/meat/coconut oil/turmeric/resveratrol etc hurt me. I can't everything promoted as healthy. Amour thyroid helps raise oxygen. MS people may not be getting thyroid medicine due to a strange TSH due to gluten hurting also the pituitary which doesn't let it make TSH. Free T4 and free T3 need to be in the upper range. My Celiac help rebuilds the cells in my brain/body to burn oxygen as it helps the gut lining heal so more nutrients absorb.  LDN helps the immune system work right..not raise/lower it...blocks hidden gluten from stimulating th opioid receptor sites which makes the immune system attack the gut lining/glands etc..

    Thanks for helping with MS! Awesome research to figure out how the immune system is working. Happiness....

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