The immune system plays a significant role in the development of various neurodegenerative diseases. In this study published in the Journal of Neuroinflammation, the role of the immune system in this disease is investigated for the first time at single-cell resolution. Natural killer (NK) cells are primarily known for their role in the defense against viral infections and tumor cells. However, this study reveals alterations in these cells in ALS patients, suggesting a possible role of NK cells in this neurodegenerative disease.
What has been done in this study?
To investigate the role of the immune system in ALS disease, blood immune cells were isolated from 14 ALS patients and 14 healthy individuals. The immune cells were analyzed using single-cell RNA sequencing, a technology that analyzes gene expression at the individual cell level. From these data, differences in cell ratio, gene expression and cell-cell communication between different immune populations were examined.
Main results
- After analyzing more than 108,000 immune cells, a significant increase in the proportion of NK cells was observed in ALS patients, especially the NK2 subpopulation, characterized by its high cytotoxic activity.
- Gene expression in NK2 cells was altered in ALS patients, andassociated with increased immune response activation and lymphocyte proliferation. In addition, these cells showed a unique pattern of cellular communication with other immune cell populations.
- There were alterations in gene expression in other immune populations, such as monocytes and CD8 T lymphocytes.
- The proportion of the CD56bright NK subpopulation, different from NK2, correlated with neurodegeneration.
Relevance of the study
This study highlights the critical role of the immune system in ALS, particularly of two NK cell subpopulations. For the first time, single-cell RNA sequencing technology has made it possible to explore the role of distinct immune populations in ALS at single-cell resolution. These findings highlight the importance of studying well-defined cell subpopulations to uncover their specific roles in the disease and design specific therapies aimed at modulating the immune system in ALS.