Immune functions of human brain pericytes and fibroblasts during neuroinflammation

Neuroinflammation, directed by microglia and astrocytes or arising as peripheral leukocyte infiltration, has adverse consequences for brain activity and is present in most neurological disorders. Mural cells (pericyte and smooth muscle cells) and perivascular fibroblasts (PVF) around them are present in the structure of CNS microvessels. These cells have important roles in BBB formation and CNS immune homeostasis. The unique perivascular position of pericytes makes these cells ideally localized to check several aspects of the CNS immune response. Under normal conditions, peripheral immune cells (lymphocytes and macrophages) do not pass into the parenchyma, during neuroinflammation; the blood-brain barrier (BBB) is crossed as a result of the infiltration of these cells into the CNS. Pericytes and other perivascular cells are highly likely to contribute to the immune-related diseases. However, the exact contribution of these cell types to is not yet known. In the light of recent studies, we can say that pericytes are very sensitive cells against CNS inflammation. What is not yet known is how these cells interact with leukocytes during neuroinflammation, how they affect neuroinflammation and how they are affected. This is an important area to be explored. Recent studies have also shown that perivascular fibroblasts are also present in perivascular space and, like pericytes, they are PDGFRβ and CD13 positive. These features make it difficult to distinguish between fibroblasts and pericytes in vascular pathology studies. In this project, we aimed to examine the roles of brain vascular pericyte and fibroblast cells in CNS inflammation. For this purpose, we stimulated the human brain primary pericyte and fibroblast cell lines with certain cytokines, and then examined the inflammatory gene expressions and protein expression changes. In addition, we conducted a chemotaxis experiment to explore the pericyte-macrophage and fibroblast-macrophage interactions. Taken together, the data defines an extensive and unappreciated contribution of brain pericytes to neuroinflammation. Since neuroinflammation occurs in almost all neurological disorders, targeting different approaches of pericyte-mediated immune responses may offer therapeutic ways for the treatment or prevention of several neurological conditions.