Help elderly T-helpers!
How to rejuvenate the immune system
Kirill Stasevich, CompulentaA protein has been found that, with age, is increasingly synthesized in immune cells and deprives them of the ability to respond to foreign molecules.
Older people are more susceptible to infectious diseases due to aging immunity. Even vaccination does not always help: if the immunity of the young "understands" 90% of vaccines, then by the age of sixty the number of effective vaccines drops by more than half, and the effectiveness of some decreases to 20%. This, of course, leads to rather sad statistics: the overwhelming number of people dying from the flu are elderly sixty–five and older.
The response to the vaccine (and to a common pathogen) depends on several types of cells. In order for the immune system to remember a stranger, immune cells must understand what his molecules look like.
To do this, there are so-called T-helpers, which present enemy molecules in the right light to other immune cells (T-killers, B-lymphocytes synthesizing antibodies, etc.). Figuratively speaking, T-helpers give others orientation to the criminal; in accordance with this orientation, B-lymphocytes, for example, will to design immunoglobulins.
In addition, T-helpers secrete substances that activate other cells. However, with age, the activity of the T-helpers themselves decreases, they begin to divide poorly and react to the appearance of foreign molecules. Moreover, in this case, neither an increase in the dose of the vaccine nor the addition of stimulant adjuvants helps. The "shock forces" of immunity may be fine, but in order to get involved in the fight against infection, they need instructions, and no one can give it.
Researchers from Stanford University Medical School (USA) have found out what prevents T-helpers from performing their functions in the elderly. In an article published in the journal Nature Medicine (Li et al., Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity), they write how the DUSP6 protein suppresses the activity of these cells. DUSP6 clears phosphate groups from a number of proteins that are involved in the activation, division and specialization of T-helpers. It accumulates with age, and the more of it, the worse the signaling pathways of immune cells work and the worse these cells react to foreign molecules-antigens.
Scientists were also able to determine the reason why DUSP6 accumulates in T-helpers. The synthesis of this protein depends on a specific regulatory microRNA (miRNA-181).
It suppresses the biosynthesis of DUSP6, but over time its content in cells decreases, reaching a minimum by the age of 65-70. If the concentration of miRNA-181 in T-helpers is increased, then the cells begin to respond adequately to the influenza vaccine. If, after that, the content of DUSP6 was artificially increased in the cells, the positive effect of miRNA-181 disappeared. The protein itself can also be affected: so, according to the authors of the study, they successfully applied the compound BCI ((E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one), which was previously used to suppress DUSP6 on heart cells to prevent cardiac hypertrophy. It turned out that the same drug works perfectly in blood cells.
It should be noted that this is not the first time researchers have encountered proteins of this family. Recently, they showed that another protein, DUSP4, had a similar effect, but it accumulated in T-helpers that had already encountered the antigen and were set up to activate immunity in response to the appearance of a strictly defined pathogen. The related protein DUSP6 affects another kind of T-helper – T-helper 0, which has not yet encountered foreign molecules.
Therefore, when dealing with a new strain of the virus, the immunity of elderly people is not able to respond to it – because of the DUSP6 protein accumulated in its cells.
Prepared based on the materials of Medical Xpress: Blocking key protein could halt age-related decline in immune system.
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