Spanish researchers have described a new molecular mechanism that favors the presentation of antigens by macrophages to CD4 T lymphocytes. This process is necessary to create effective immune and memory responses and is also relevant in the rejection of transplants and in autoimmune diseases. The study was led by Cristina López-Rodríguez and Jose Aramburu, scientists from the Department of Experimental Sciences and Health (DCEXS) of the Pompeu Fabra University (UPF).
Macrophages are cells of the immune system that act as sensors within the tissues of the body. In this way, they regulate the integrity of the tissues both to facilitate their functioning under normal conditions and when there is a disease.
One of the functions of macrophages is to present the antigens they find in tissues —which are external substances that can trigger an immune reaction— to T lymphocytes. This process is necessary to create effective immune and memory responses and also it is relevant in the rejection of transplants and in autoimmune diseases.
In the new study, published in the Journal of Experimental Medicine, the team of researchers describes a new molecular mechanism that favors the presentation of antigens by macrophages to CD4 T lymphocytes. Specifically, they have discovered that the genes that are responsible for expressing the antigen presenting molecules in macrophages are activated by the NFAT5 protein.
New functions of the protein
NFAT5 is a protein known mainly for its function in adapting cells to high salinity environments. Recent studies by the UPF group have revealed new functions of this protein, such as the regulation of gene expression in immune cells in different contexts.
They used skin grafts in mice as a model of transplantation because the presentation of antigens is part of the process of rejection of transplants from one organism to another. On one hand, in normal mice, rejection occurred when they had skin tissue transplant from another mouse. However, in cases where the donor rodents had NFAT5-deficient macrophages, the grafts survived longer.
“Our results, in agreement with what we observed in the in vitro tests, show that by eliminating NFAT5, the communication between macrophages and T lymphocytes is interrupted, so the latter are not activated, and therefore the rejection of skin transplants is attenuated,” said the authors.
This study has also involved scientists from the Center for Biological Research, the National Center for Cardiovascular Research, the Complutense University of Madrid and the Biomedical Research Park and the Science Park of Barcelona.