A Protein for Strengthening Thymic Activity
I n the AV短视频 (UNIGE) Faculty of Medicine鈥檚 Pathology and Immunology Department, researchers are emphasizing the catalytic role that the CYR61 protein plays in the thymus鈥攈eadquarters of immune cell development. The experiments involving this protein led to an appreciable increase in the production of these cells, the T lymphocytes. The results of this research are the subject of an article in the latest edition of the journal Nature Communications.
The thymus is a strange organ. It is discreetly housed at the bottom of the throat, and its swollen shape is characteristic of a dish loved by foodies: veal sweetbreads. Beat Imhof, professor in the UNIGE Faculty of Medicine鈥檚 Pathology and Immunology Department, smilingly said that its role is equivalent to an 鈥渋mmune cell school鈥�. A school of hard knocks, as the thymus is where the T lymphocytes are trained to kill pathogens.
A protein that stimulates cell proliferation
In Professor Imhof鈥檚 laboratory, researcher Yalin Emre noticed that the CYR61 protein, known in scientific literature to promote cell proliferation (including cancer cells), is expressed by epithelial cells in the thymus. In other words, the thymus produces the CYR61 protein. What connection does the protein have with its neighbors inside the organ? Yalin Emre鈥檚 research has highlighted its affinities with the T lymphocytes and the thymic stroma cells, on to which it attaches.
A positive effect on thymic cells
Research continued on tissue culture, then in vivo on mice, confirming the protein鈥檚 two roles: promoting the proliferation of thymic epithelial cells, and fostering their contact with immature T lymphocytes developing in the thymus.
Finally, with the intent to utilize the CYR61鈥檚 capacity in a healthy environment, researchers administered the protein to thymi in vitro. Those organs developed significantly. Their stromal cells proliferated, inflating the volume of the thymi. The same result was observed in vivo, on thymi treated with the protein, and which had been transplanted on mice without thymi. The capacity of transplanted organs to recruit hematopoietic stem cells increased, and consequently, the production of developing T lymphocytes increased as well. The quantity of forming immune cells doubled compared to those produced by a non-stimulated thymus. However, the phenomenon occurred in a very proportional way, because in both the stroma and the lymphocytes, the individual development capacity of cells that came into contact with the CYR61 protein remained identical to that of cells present in a natural thymus.
From immature cells to T lymphocytes, expert killers
These observations open up interesting prospects for strengthening the thymus, which plays a key role in our immunity. In fact, after passing through this organ, the hematopoietic stem cells born in our bone marrow are transformed into T lymphocytes, i.e. they are equipped with an ad hoc receiver that will help each one of them recognize only one type of molecule to hunt down. If, among these molecules, there are some that are part of our own body鈥斺�渢he self鈥濃�攖he thymus is tasked with deactivating the developing T lymphocytes susceptible of killing the self. In wartime, during an infection, it鈥檚 a race against time between the production of immune cells and pathogens, which multiply and seek to take control of our cells in order to reproduce at full speed.
A key organ in the fight against infections, the thymus works in two steps: first, it produces enormous amounts of so-called 鈥渋mmature鈥� cells; then, among these immature cells, the thymus delegates to its stroma cells鈥攊ts own constitutive cells鈥攖he responsibility of selecting the ones capable of distinguishing the 鈥渘on-self鈥�, so that once they are released into the bloodstream, they can efficiently attack each of their corresponding pathogens.
Age, strengths, and weaknesses of the thymus
But with age, and immediately after puberty, the thymus diminishes then shrivels. Yet it remains active throughout the entire life of a human being鈥攁 life that tends to be increasingly long in rich countries. With the aging of the population, it is advantageous for industrialized societies to look into ways of preventing infections that prey on weaker organisms, such as the chronically ill and the elderly. With certain genetic diseases, the blood cells that form in bone marrow鈥攖he famous hematopoietic stem cells鈥攁re unable to distinguish the T lymphocytes, even after their trip through the thymus. Strengthening the thymus and curbing its natural degeneration could therefore help offset some deficiencies.
Therapeutic possibilities
In cultivation, CYR61鈥檚 catalytic strength was only observed on the epithelial cells of the thymic stroma. In vivo, transplants of thymus lobes treated with the protein increased the organ鈥檚 volume and caused a noticeable increase of T lymphocytes in the blood of immunodeficient mice. The treated and transplanted thymus functioned normally, i.e. its cells did not exhibit anarchic development. Such findings portend promising possibilities regarding therapeutic research aimed at countering thymic obsolescence.
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23 Jul 2015