Vindictive cells
"Memory" of Bone Marrow Stem Cells May Support Inflammation
Trouble does not go alone, people say, and some diseases often occur together. It is known that one patient may have a combination of different chronic inflammatory diseases that are pathogenetically related, and recently researchers have studied the mechanism of this phenomenon.
The immune system has such a property as immunological memory – the ability to quickly and effectively initiate an immune response in response to a repeated encounter with the same antigen (a substance that the body considers as foreign or dangerous). This is good in the case of viral or bacterial antigens, but the immune system can also remember its reaction to internal factors associated, for example, with chronic inflammation. And this is bad: such a "memory" will contribute to the reproduction of the pathological process.
Immune memory is usually understood as T- and B-memory cells related to acquired immunity. However, not so long ago it was discovered that there is also a memory of innate immunity associated with neutrophils and monocytes – myeloid blood cells. By participating in the fight against infection and in the development of inflammation, these cells can "remember" their condition and react more actively to a similar threat.
Recently, an international group of scientists conducted experiments on laboratory mice that were caused by periodontitis – an inflammatory gum disease. Periodontitis was chosen as a model of the inflammatory process for a reason, since a rather mysterious connection between this pathology and the risk of developing a number of diseases, from rheumatoid arthritis, pneumonia and diabetes to cardiovascular diseases, some types of cancer and Alzheimer's disease, has long been established.
It turned out that the reaction to inflammation is "remembered" by hematopoietic stem cells of the bone marrow – precursors of myeloid blood cells. The bone marrow is the main hematopoietic organ, and stem cells are able to quickly respond to problems by changing the "output" of the necessary differentiated cells. At the same time, it turned out that such a memory is formed due to epigenetic changes that do not affect the DNA sequence, but affect the parameters of the "on" and "off" genes (in our case, associated with inflammation).
The process, as a result of which a "conveyor" of the production of hyperreactive immune blood cells appears, can be triggered not only by periodontitis, but also by any disease accompanied by inflammation. Such cells will actively move to inflamed tissues, contributing to the exacerbation of the pathological process. This is probably how a positive feedback is formed between their cellular precursors – stem "memory cells", and the development of inflammation.
A drawing from the University of Pennsylvania press release How one inflammatory disorder exacerbates another - VM.
The researchers confirmed their findings experimentally by transplanting the bone marrow of periodontitis patients to healthy mice. And when joint inflammation (arthritis) was caused in these mice a few months after transplantation, it was more severe in them than in individuals who had bone marrow transplanted from healthy donors.
In another series of experiments, scientists have shown that a key role in the formation of "inflammatory memory" is played by a molecular signaling pathway controlled by the pro-inflammatory cytokine receptor interleukin 1 (IL-1). In mice in which this signaling pathway was "turned off", the "memory" of hematopoietic stem cells was not formed.
From the results of this work, the researchers themselves draw two practical conclusions. Firstly, it is possible to mitigate the negative effects of "inflammatory memory" by blocking the work of the IL-1 receptor. Secondly, it is necessary to revise the criteria for choosing bone marrow donors in order not to expose recipients to an increased risk of inflammatory diseases.
Article by Li et al. Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities is published in the journal Cell.
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