Amazing stuff!
"The human immune system is a nearly perfect defense mechanism. It protects the body from disease-causing bacteria, viruses, and other pathogens. It detects nascent tumors and eradicates them. It cleans up cellular debris at the site of injury or infection.
To perform its myriad functions, the immune system must, above all, differentiate between self and non-self—a remarkable selective ability that allows it to detect and disable harmful agents while sparing the body’s own tissues. ...
The research shows that the thymus gland—the organ where T cells are born and trained—educates nascent immune cells by exposing them to proteins made by thymus cells that mimic various tissues throughout the body. Specifically, the research demonstrates that by assuming different identities, these specialized thymus cells preview for the maturing T cells self-proteins they would encounter once they leave their native thymus gland. ..."
From the abstract:
"Medullary thymic epithelial cells (mTECs) ectopically express thousands of peripheral-tissue antigens (PTAs), which drive deletion or phenotypic diversion of self-reactive immature T cells during thymic differentiation. Failure of PTA expression causes multiorgan autoimmunity. By assaying chromatin accessibility in individual mTECs, we uncovered signatures of lineage-defining transcription factors (TFs) for skin, lung, liver, and intestinal cells—including Grhl, FoxA, FoxJ1, Hnf4, Sox8, and SpiB—in distinct mTEC subtypes. Transcriptomic and histologic analyses showed that these subtypes, which we collectively term mimetic cells, expressed PTAs in a biologically logical fashion, mirroring extra-thymic cell types while maintaining mTEC identity. ... Expression of a model antigen in mimetic cells sufficed to induce cognate T cell tolerance. ..."
Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells (no public access)
Thymus gland
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