As published in a recent study, researchers have discovered that neural stem cells are impeded by the invasion of T cells, immune cells that are not normally present in the neural stem cell niche [1].
The neural stem cell niches
Our brains contain neural stem cells (NSCs); like their name suggests, these cells are responsible for the formation of new neurons within the brain. This process, which continues throughout life, is known as neurogenesis. These stem cells live in particular niches, which contain a panoply of different cell types, including stem cells in different phases of development and multiple types of immune cells. However, the researchers discovered a startling fact: the brains of older mice contain many specific immune cells known as T cells, while the brains of younger mice contain very few – and, as the study explains, this is true for humans as well.
T cells and interferon-γ
NSCs have receptors for a signaling molecule called interferon-γ, which discourages them from performing their normal function, and the researchers suggest that this is likely to be the main reason why they fail to proliferate in aged brains. The invading T cells, which express interferon-γ, proliferate through clonal expansion; the researchers mention that this particular method of cellular reproduction is normally done in response to the presence of an antigen, a harmful molecule that causes immune cells to react. If there is such an antigen in the brains of aged mammals, what it is and why it is there are questions that have yet to be answered.
Abstract
The mammalian brain contains neurogenic niches that comprise neural stem cells and other cell types. Neurogenic niches become less functional with age, but how they change during ageing remains unclear. Here we perform single-cell RNA sequencing of young and old neurogenic niches in mice. The analysis of 14,685 single-cell transcriptomes reveals a decrease in activated neural stem cells, changes in endothelial cells and microglia, and an infiltration of T cells in old neurogenic niches. T cells in old brains are clonally expanded and are generally distinct from those in old blood, which suggests that they may experience specific antigens. T cells in old brains also express interferon-γ, and the subset of neural stem cells that has a high interferon response shows decreased proliferation in vivo. We find that T cells can inhibit the proliferation of neural stem cells in co-cultures and in vivo, in part by secreting interferon-γ. Our study reveals an interaction between T cells and neural stem cells in old brains, opening potential avenues through which to counteract age-related decline in brain function.
Conclusion
This particular study has discovered a possibly vital part of why neural stem cells in aging brains fail to proliferate, even though the reason for the T cell invasion remains unknown and the full relationship between the immune system and NSCs has not yet been studied. However, by simply announcing the fact of their presence, this study has opened the door to new lines of research in this area, which may one day lead to therapies that block the effects of interferon-γ, discourage T cells from invading NSC niches, or remove the fundamental reason why T cells invade such niches at all.
Literature[1] Dulken, B. W., Buckley, M. T., Negredo, P. N., Saligrama, N., Cayrol, R., Leeman, D. S., … & Wyss-Coray, T. (2019). Single-cell analysis reveals T cell infiltration in old neurogenic niches. Nature, 1.
