Immune complexity: autoimmunity protections (Introduction)

by David Turell , Thursday, July 02, 2020, 20:31 (1388 days ago) @ David Turell

Certain molecules are involved:

https://medicalxpress.com/news/2020-07-protein-autoimmunity.html

"The immune system is supposed to protect from external microbial invaders, but sometimes it turns its efforts inward, potentially resulting in autoimmune diseases. In a new study, researchers from Osaka University have discovered how reversible modifications to DNA by certain proteins protect from autoimmune diseases, and conversely, how the absence of these proteins paves the way to autoimmunity.

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"An important regulatory mechanism is the reversible addition (methylation) or removal (demethylation) of chemical bonds, so-called methyl groups, to segments of DNA. This modifies the readout of DNA segments. Proteins of the ten-eleven translocation (Tet) family are known DNA demethylases, which decrease the production of certain proteins in immune cells. How Tet proteins play into the development of autoimmune diseases has remained unknown until now.

"'Epigenetics deals with how reversible changes in DNA affect gene activity and protein expression," says corresponding author of the study Tomohiro Kurosaki. "Disrupting this machinery can have dramatic effects on cellular function. The goal of our study was to understand how epigenetic control in a specific type of immune cells, called B cells, affects the development of autoimmune diseases."

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"'These findings suggest that Tet2 and Tet3, as well as proteins whose expression is regulated by Tet2 and Tet3, might play a fundamental role in the development of systemic lupus erythematosus," says lead author of the study Shinya Tanaka. "We wanted to gain a deeper molecular understanding of the mechanism behind the effects of Tet2 and Tet3 on the immune system."

"The researchers next investigated a different type of immune cell, called T cells, which often interact with B cells, and found that T cells were excessively activated in the Tet2/Tet3 knockout mice. By examining the molecular interaction between B and T cells closer, the researchers found that the protein CD86 was produced at higher levels in B cells of Tet2/Tet3 knockout mice, leading to aberrant T cell activation and autoimmunity.

"'These are striking results that show how Tet proteins suppress autoimmune diseases by inactivating B cells and thus ultimately preventing them from attacking our bodies," says Kurosaki. "Our findings provide new insights into the contribution of epigenetics to the development of autoimmune disease. Regulating Tet proteins and their downstream effectors could be a novel treatment for autoimmune diseases.'"

Comment: Our immune system should not attack us, but it does under some circumstances which are mistakes by the control systems. The mistakes are that the protections put in place do not work.