JEM deep interpretation! Why can a small mutation have a very large effect on the properties of T cells?

October 13, 2020 // -- T-cells play a key role in the functioning of the human immune system, effectively distinguishing diseases or foreign bodies from the body's own healthy tissues with high accuracy, while also inducing the necessary action to deal with some foreign invasions, details of which are varied, but researchers do not yet understand every step of the way.
, scientists from institutions such as the University of Welzburg revealed these processes in a study published in the international journal Journal of Aeronology Medicine entitled "Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity". In new details, the researchers found that tiny point mutations in genes may modify T-cells to make them less protective, although this may be an advantage after stem cell transplants, including infusions of T-cells, to help control serious side effects in the patient's body.
When T cells detect foreign or altered tissue, they induce an immune response, such as infected or tumored tissue, usually through a subject on the surface of their cells, which then send signals to the inside of the cell to initiate an immune response;
NFAT is made up of multiple family members who may have overlapping tasks or perform completely different functions, but this doesn't seem to be all, like many other proteins in cells that can still be modified to customize their functionality after synthesis, and in a recently published study, researchers studied a special modification of members of the NFATc1 family, known as SUMOylation.
researcher Friederike Berberich-Siebelt explains that ubibin-like modification plays a key role in different cellular processes, such as nuclear transport, programmed cell death, or antiviral mechanisms, and that researchers have observed the absence of ubibin modification processes in a variety of diseases, such as cancer and herpes virus infection.
Photo Source: CC0 Public Domain In this study, researchers studied experimental animals that had two virtually trivial point mutations in the NFATc1 gene, but these mutations blocked the occurrence of ubics, which may not necessarily be a disadvantage, the researchers said. The offspring are perfectly healthy, and modified NFATc1 even mediates specific signaling path pathlines, reducing the occurrence of clinical symptoms of multiple sclerosis at least in animal models, which are much less aggressive to host animal body tissue when using T cells carrying these mutations during stem cell transplantation.
this effect is due to an increase in the level of lecirtin-2 at the beginning of the immune response at the biomolesic level, which can counteract the process of T differentiation into inflammatory T-cell subtypes and also support the production of so-called regulatory T-cells, which The study found that later scientists had important effects on stem cell transplants, including T-cell infusions, and the researchers said that when NFATc1 was not ubially modified T-cells, it was effective in preventing side effects, suggesting that point mutations may have a greater impact.
In order to conduct more detailed studies, the researchers will continue to study the possibility and feasibility of treatment later, and the researchers will also want to know whether CRISPR/Cas9 gene editing techniques can be used to edit human T-cells to make them exhibit just the right activity during the hematopoietic stem cell transplant process.
The results of this paper may be independent of the potential consequences of therapeutic applications, and the researchers concluded that we are very interested in understanding the mechanisms of fine regulation in cells, such as T-cellular sensor signals and the function of members of the NFAT family and their subsypes.
In fact, two harmless point mutations and subtle direct effects may be enough to flip the switch from inflammation, autoimmunity, and rejection to the body's tolerance, and a small shift in focus may be enough at the beginning of the immune response.
() Reference: 1 Yin Xiao et al. Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity, Journal of Aeronitration (2020). DOI: 10.1084/jem.20181853 (2) A small T cell switch with a big impactby Julius-Maximilians-Universites-Würzburg.