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Stroke strikes and kills, always so caught off guard, this is also a major reason why it has become the greatest threat to Chinese people's health.
Even if they can save their lives, stroke survivors have to face a long and difficult road.
It is not easy to recover from various dysfunctions caused by ischemic necrosis of brain tissue.
Singularity Cake has recently witnessed the recovery of the elders in the family, and every bit of progress has not come easily.
This makes Singularity Cake think of the old question that I had in school: Can there be a therapy to promote the recovery of stroke patients? A recent study by Chinese scientists may point to a feasible direction: The team of Assistant Professor Hu Xiaoming (transliteration) from the University of Pittsburgh found that regulatory T cells that infiltrate the brain within a few weeks after a stroke can repair the white matter of the brain Has a key role, thereby affecting the rehabilitation of neurological function and the long-term prognosis of patients.
Regulatory T cells, are you familiar with it? (Image source: NIH image group) Regulatory T cells secrete osteopontin to enhance the repair activity of microglia, thereby promoting brain white matter repair and oligodendrocytes.
In animal experiments, new immunotherapy is used to increase the number of regulatory T cells, which helps to restore neurological function after stroke [1].
The research was published on Immunity.
In case of undecided problems, it may be a little exaggerated to turn to immunology, but the immune system undoubtedly plays a very important role in the process of nerve repair and regeneration.
Among them, the more studied T cell subsets are this time.
The protagonist-regulatory T cells.
Although in tumor immunotherapy, regulatory T cells are about to become cross-street mice, and everyone shouts, but its immunosuppressive effect is very useful for controlling inflammatory damage in central nervous system diseases, and studies have found that it is regulatory.
T cells can directly promote remyelination [2].The neuroprotection and regeneration mechanism of regulatory T cells (picture source: Nature Reviews Neurology).
In terms of stroke treatment and rehabilitation, a study published in Nature in 2019 showed that regulatory T cells are "late but arrival "They will begin to infiltrate the damaged part one or two weeks after the stroke, and they will show different gene expression from similar cells in other parts of the body [3].
Acute ischemic injury is basically over after 1-2 weeks after the stroke, and it begins to enter the chronic recovery period, so it is time for regulatory T cells to come, but this only shows that they "have the potential to promote brain recovery.
" As for their specific What they are doing is the problem that Professor Hu Xiaoming's team has to clarify this time.
The research team performed a comprehensive single-cell sequencing of the immune cells that infiltrated the brain within 5-14 days after the stroke on a mouse model of stroke, and found that by the 14th day, the adaptive immune cells had already accounted for the majority, including CD4+ Regulatory T cells, as well as CD8+ effector T cells, NKT cells and so on.
If the regulatory T cells in the stroke mice are selectively eliminated, the blood flow and perfusion status of the brain of the mice will be significantly reduced, the performance of cognitive functions will become worse, and the long-term sensorimotor function after stroke will be affected, without stroke.
Of mice were unaffected after clearing regulatory T cells.
The classification of immune cells that infiltrate the brain, and the effect of knocking out regulatory T cells to clear the regulatory T cells in mice in advance, and then injecting them in the acute ischemic injury period after the stroke, will not affect the white matter of the brain The integrity after stroke has a significant impact.
In other words, regulatory T cells do not participate in saving and protecting the brain in the acute phase, but promote repair after injury and clean up the mess.
Further experiments have shown that the osteopontin secreted by regulatory T cells is the key to Crosstalk between them and the microglia in the brain.
Under the influence of regulatory T cells, microglia will become anti-inflammatory and repair-promoting Subtype transformation.
Next, the microglia will affect the oligodendrocyte progenitor cells, prompting them to differentiate into mature oligodendrocytes, which accelerates oligodendrogenesis, which is essential for the repair of white matter in the brain It is of great significance.
To further amplify the role of regulatory T cells in this pathway, the first method that comes to mind is to make them more.
The research team injected an antibody complex composed of interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody, and found that repeated injections after stroke can effectively increase the number of regulatory T cells.
With the increase in the number of regulatory T cells, the various neurological functions of the mice have also been significantly restored.
The analysis of the brain also suggests that the integrity of the white matter is better.
It can be said that the antibody complexes are preliminary in terms of restoring neurological function and improving long-term prognosis.
Well done.
The whole process of the whole regulation mechanism Professor Hu Xiaoming said that there are still many problems to be solved if this set of therapy is used in clinical treatment.
On the one hand, we can try to further transform the antibody complex to reduce the side effects of treatment, and on the other hand, it is similar to adoptiveness.
Attempts of cell therapy, individualized tailored regulatory T cells, and then injected into patients after stroke.
The treatment of acute ischemic stroke must race against time so as not to miss the golden time window for thrombolysis, but this idea of using immune cells to promote long-term recovery is certainly not so time-consuming.
But Singularity Cake really hopes that related research can be carried out faster.
There are too many stroke patients and family members who are eagerly waiting for such treatment. References: 1.
Shi L, Sun Z, Su W, et al.
Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke[J].
Immunity, 2021.
2.
Hu X, Leak RK, Thomson AW, et al.
Promises and limitations of immune cell-based therapies in neurological disorders[J].
Nature Reviews Neurology, 2018, 14(9): 559-568.
3.
Ito M, Komai K, Mise-Omata S, et al.
Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery[J].
Nature, 2019, 565(7738): 246-250.
The author of this article | Tan Shuo
Even if they can save their lives, stroke survivors have to face a long and difficult road.
It is not easy to recover from various dysfunctions caused by ischemic necrosis of brain tissue.
Singularity Cake has recently witnessed the recovery of the elders in the family, and every bit of progress has not come easily.
This makes Singularity Cake think of the old question that I had in school: Can there be a therapy to promote the recovery of stroke patients? A recent study by Chinese scientists may point to a feasible direction: The team of Assistant Professor Hu Xiaoming (transliteration) from the University of Pittsburgh found that regulatory T cells that infiltrate the brain within a few weeks after a stroke can repair the white matter of the brain Has a key role, thereby affecting the rehabilitation of neurological function and the long-term prognosis of patients.
Regulatory T cells, are you familiar with it? (Image source: NIH image group) Regulatory T cells secrete osteopontin to enhance the repair activity of microglia, thereby promoting brain white matter repair and oligodendrocytes.
In animal experiments, new immunotherapy is used to increase the number of regulatory T cells, which helps to restore neurological function after stroke [1].
The research was published on Immunity.
In case of undecided problems, it may be a little exaggerated to turn to immunology, but the immune system undoubtedly plays a very important role in the process of nerve repair and regeneration.
Among them, the more studied T cell subsets are this time.
The protagonist-regulatory T cells.
Although in tumor immunotherapy, regulatory T cells are about to become cross-street mice, and everyone shouts, but its immunosuppressive effect is very useful for controlling inflammatory damage in central nervous system diseases, and studies have found that it is regulatory.
T cells can directly promote remyelination [2].The neuroprotection and regeneration mechanism of regulatory T cells (picture source: Nature Reviews Neurology).
In terms of stroke treatment and rehabilitation, a study published in Nature in 2019 showed that regulatory T cells are "late but arrival "They will begin to infiltrate the damaged part one or two weeks after the stroke, and they will show different gene expression from similar cells in other parts of the body [3].
Acute ischemic injury is basically over after 1-2 weeks after the stroke, and it begins to enter the chronic recovery period, so it is time for regulatory T cells to come, but this only shows that they "have the potential to promote brain recovery.
" As for their specific What they are doing is the problem that Professor Hu Xiaoming's team has to clarify this time.
The research team performed a comprehensive single-cell sequencing of the immune cells that infiltrated the brain within 5-14 days after the stroke on a mouse model of stroke, and found that by the 14th day, the adaptive immune cells had already accounted for the majority, including CD4+ Regulatory T cells, as well as CD8+ effector T cells, NKT cells and so on.
If the regulatory T cells in the stroke mice are selectively eliminated, the blood flow and perfusion status of the brain of the mice will be significantly reduced, the performance of cognitive functions will become worse, and the long-term sensorimotor function after stroke will be affected, without stroke.
Of mice were unaffected after clearing regulatory T cells.
The classification of immune cells that infiltrate the brain, and the effect of knocking out regulatory T cells to clear the regulatory T cells in mice in advance, and then injecting them in the acute ischemic injury period after the stroke, will not affect the white matter of the brain The integrity after stroke has a significant impact.
In other words, regulatory T cells do not participate in saving and protecting the brain in the acute phase, but promote repair after injury and clean up the mess.
Further experiments have shown that the osteopontin secreted by regulatory T cells is the key to Crosstalk between them and the microglia in the brain.
Under the influence of regulatory T cells, microglia will become anti-inflammatory and repair-promoting Subtype transformation.
Next, the microglia will affect the oligodendrocyte progenitor cells, prompting them to differentiate into mature oligodendrocytes, which accelerates oligodendrogenesis, which is essential for the repair of white matter in the brain It is of great significance.
To further amplify the role of regulatory T cells in this pathway, the first method that comes to mind is to make them more.
The research team injected an antibody complex composed of interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody, and found that repeated injections after stroke can effectively increase the number of regulatory T cells.
With the increase in the number of regulatory T cells, the various neurological functions of the mice have also been significantly restored.
The analysis of the brain also suggests that the integrity of the white matter is better.
It can be said that the antibody complexes are preliminary in terms of restoring neurological function and improving long-term prognosis.
Well done.
The whole process of the whole regulation mechanism Professor Hu Xiaoming said that there are still many problems to be solved if this set of therapy is used in clinical treatment.
On the one hand, we can try to further transform the antibody complex to reduce the side effects of treatment, and on the other hand, it is similar to adoptiveness.
Attempts of cell therapy, individualized tailored regulatory T cells, and then injected into patients after stroke.
The treatment of acute ischemic stroke must race against time so as not to miss the golden time window for thrombolysis, but this idea of using immune cells to promote long-term recovery is certainly not so time-consuming.
But Singularity Cake really hopes that related research can be carried out faster.
There are too many stroke patients and family members who are eagerly waiting for such treatment. References: 1.
Shi L, Sun Z, Su W, et al.
Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke[J].
Immunity, 2021.
2.
Hu X, Leak RK, Thomson AW, et al.
Promises and limitations of immune cell-based therapies in neurological disorders[J].
Nature Reviews Neurology, 2018, 14(9): 559-568.
3.
Ito M, Komai K, Mise-Omata S, et al.
Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery[J].
Nature, 2019, 565(7738): 246-250.
The author of this article | Tan Shuo
