구조 세포와 면역반응의 관계

모르는 단어

hematopoietic:

upregulation: in the biological context of organism's production of gene products, 

downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. the complementary process that involves increases of such components is called upregulation.

epigenetics: 유전자 자체에서의 변화가 아닌, 유전자 발현에서의 변화로 인한 phenotype의 변화

 

In a Nature paper, CeMM researchers report on the epigenetic and transcriptional regulation in structural cells. They found widespread activity of immune genes, suggesting that structural cells are deeply involved in the body's response to pathogens. Moreover, the study uncovered an epigenetic potential that pre-programs structural cells to engage in the immune response against pathogens. These findings highlight an underappreciated part of the immune system and open up an exciting area for research and future therapies.

Much of this protection is provided by hematopoietic immune cells, which are derived from the bone marrow and specialize in fighting pathogens. They include macrophages, which remove pathogens; T cells, which kill infected virus-producing cells; and B cells producing antibodies that neutralize pathogens. However, immune functions are not restricted to these 'specialists,' and many more cell types are able to sense when they are infected and contribute to the immune response against pathogens.

 epithelial cells constitute the surface of the skin, while also separating tissues and organs from each other; endothelial cells coat the inside of all blood vessels; and fibroblast provide the connective tissue that keeps tissues and organs in shape. Structural cells are often regarded as simple and rather uninteresting components of the body, despite their well-established roles in autoimmune diseases (such as rheumatoid arthritis and inflammatory bowel disease) and in cancer.

 the CeMM researchers established a comprehensive catalog of immune gene activity in structural cells, applying high-throughput sequencing technology (RNA-seq, ATAC-seq, ChIPmentation) to three types of structural cells (epithelium, endothelium, fibroblasts) from 12 organs in healthy mice.

Interestingly, many immune genes showed epigenetic signatures that are normally associated with high gene expression, while the observed expression in structural cells obtained from healthy mice was lower than expected based on their epigenetic signatures. CeMM researchers therefore hypothesized that these genes are epigenetically pre-programmed for rapid upregulation when their activity is needed—for example in response to a pathogen. 

When the mice were infected with a virus (LCMV) that triggers a broad immune response, many of those genes that were epigenetically poised for activation became upregulated and contributed to the transcriptional changes that structural cells showed in response to viral infection. These results suggest that structural cells implement an "epigenetic potential" that pre-programs them to engage in rapid immune responses. As an additional validation, the researchers triggered an artificial immune response by injecting cytokines into mice, and they indeed found that many of the same genes were upregulated.

 

reference

Structural cells are key regulators of organ-specific immune responses, Nature (2020). DOI: 10.1038/s41586-020-2424-4 , www.nature.com/articles/s41586-020-2424-4