Brain-invading T cells as regulators of microglial function in stroke
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
Stroke is one of the leading causes of death and is the third cause of long-term disabilities worldwide. The body's inflammatory response to stroke is a critical factor in the development and progression of the neurological deficits. The inflammatory response occurs quickly after stroke and involves the activation of microglial cells (the resident immune cells in the brain) and the invasion of peripheral immune cells. Microglial cells react quickly to acute brain injury by sensing molecules released from dying neurons, and microglia have been shown to contribute to both long-term neuronal injury and repair after stroke. After initial glial cell activation, there is an increase in cerebral cytokine, chemokine, and adhesion molecule expression, leading to the recruitment of peripheral leukocytes to the lesion site. Among peripheral leukocytes invading the injured brain T cells, a type of lymphocytes, have been identified as having the largest impact on exacerbating brain damage after stroke. Recent research has confirmed the effectiveness of blocking T cell invasion in improving stroke outcomes in mice. However, some T cell subpopulations, such as regulatory T cells, have been shown to provide neuroprotective functions. But how T cells, and in particular regulatory T cells, affect the development of the brain damage is not fully understood. While microglia have been viewed as antigen-presenting and costimulatory cells leading to T cell activation, the impact of T cells on microglial activation has not been well known in the context of stroke. Therefore, in this research project, we sought to understand how brain-invading T cells influence microglial function and what the effects are on stroke progression. When someone has a stroke, their brain becomes inflamed, causing further damage to the brain. While T lymphocytes are only present in small numbers in the brain, they have been found to contribute the most to this inflammation. In this study, we used mice to look at how different types of T cells affect the activation state of microglia after a stroke. Using state-of-the-art technologies, we were able to highlight that different types of T cells can control the way microglia behave, and that some T cells (the regulatory T cells) can even change the way microglia work to help the brain recover after a stroke. This research could lead to new ways of treating stroke by targeting the interaction between T cells and microglia to control inflammation in the brain. Overall, our findings contribute to our understanding of the complex immune responses that occur in the brain following ischemic stroke and highlights the potential of immune-based therapies for treating this devastating condition. This study was recently published in the peer-reviewed eLife journal.
Publications
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T cells modulate the microglial response to brain ischemia. Cold Spring Harbor Laboratory.
Benakis, Corinne; Simats, Alba; Tritschler, Sophie; Heindl, Steffanie; Besson-Girard, Simon; Llovera, Gemma; Pinkham, Kelsey; Kolz, Anna; Theis, Fabian; Gökce, Özgün; Peters, Anneli & Liesz, Arthur
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T cells modulate the microglial response to brain ischemia. eLife, 11.
Benakis, Corinne; Simats, Alba; Tritschler, Sophie; Heindl, Steffanie; Besson-Girard, Simon; Llovera, Gemma; Pinkham, Kelsey; Kolz, Anna; Ricci, Alessio; Theis, Fabian J.; Bittner, Stefan; Gökce, Özgün; Peters, Anneli & Liesz, Arthur
