How to help helpers?
Human follicular T-helpers were picked up by a "leader protein"
Denis Strigun, Naked Science
Scientists from the Institute of Allergy and Immunology in La Jolla (USA) have discovered a protein from the cytokine group that plays a crucial role in the maturation of follicular T-helper immune system – Tfh cells. This is written by Nature Immunology (Locci et al., Activin A programs the differentiation of human T FH cells).
Tfh cells are a subpopulation of T helper cells that help immune B cells produce antibodies and neutralize pathogens. It is expected that manipulations with Tfh cells will stimulate an immune response of a higher quality - this is the basis for the work of vaccines. In early studies, scientists were able to identify differentiation factors of this subpopulation in mice, but the mechanism could not be reproduced in humans.
As part of the new experiment, the researchers analyzed a library of 2,000 "human" proteins associated with the maturation of Tfh cells using high-performance screening. The most optimal candidate for the role of a leader in this process was the secreted protein activin A. Tests showed that in the presence of immature Tfh cells, activin A includes the expression of genes encoding receptors and other factors characteristic of mature cells. At the same time, the protein was localized in the lymphoid tissue of the tonsils, where Tfh cells differentiated in close proximity to B cells - indirectly indicating that activin A was produced in the "right place".
Further studies confirmed that activin A stimulation was accompanied by maturation of follicular T-helper cells in primates, but not in rodents.
Follicles (from Lat. folliculus, "pouch") – rounded formations in various organs. Their inflammation in the tonsils is called follicular angina – VM.
In addition, the effectiveness of activin A depended on whether the downstream DNA-binding proteins SMAD2 were involved/3. So, the introduction of the drug Galunisertib, which silences SMAD2, made the cells insensitive to the signals of activin A. Thus, it was found that a drug potentially capable of blocking T-helpers and keeping Tfh cells in an immature state already exists.
"Many autoimmune diseases involve excessive formation of Tfh cells, which can provoke the production of autoreactive antibodies. In at least two cases – rheumatoid arthritis and systemic lupus erythematosus – the level of activin A in the blood is higher than normal, which suggests that in these diseases the protein is involved in the violation of differentiation of Tfh cells," said Dr. Michela Lozzi (in a press release LJI researchers reveal dominant player in human T helper cell maturation – VM).
In the near future, scientists intend to work on creating a technique for the directed growth of follicular T-helpers. It is assumed that this will help to achieve a more intensive response of B cells when an infection is detected, as well as to reproduce cells with a long memory to fix and maintain the necessary level of Tfh cells in the body.
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08.07.2016