Good Article Review About Mtec Maturation:

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Article Review

The subsequent text contains a review on the article published on the role of Autoimmune Regulator (AIRE). The article focused on the various pathways which leading to tolerance induction and described them in detail. The authors also illustrate the role of AIRE deficiency and development of autoimmunity due to its core participation in tolerance induction. It also leads to faulty negative selection and states that effective removal of autoreactive cells is solely relying on presence of AIRE. The article also stated that AIRE is principally expressed in major histocompatibility complex (MHC) class II-high and CD80-high medullary thymic epithelial cells (mTECs). AIRE forms promyelocytic leukemia(PML) nuclear bodies that are associated with structural modulation of chromatin, control of transcription, DNA repair and response to antiviral.
Role of AIRE as a master regulator of tissue-specific antigens (TSAs) has been widely studied but it is not the only mechanism involved in development of central tolerance. These additional mechanisms are mTEC maturation, chemokine expression, induction of regulatory T-cells and other mechanisms.

mTEC has to pass several stages of development and has various subpopulations like low and high MHC. Evidence is obtained that shows that loss of Aire alters the basic morphology of the mTEC.

Chemokine Expression:

Lack of chemokine receptor caused faulty tolerance induction and infiltration of peripheral tissues with autoantibodies. The authors reported down-regulation of all chemokine cells in post-aire cells.

Induction of Treg:

mTECs are theorized to contribute to production of central tolerance by the induction of naturally occurring Tregs. The authors stated that aire expression is a pre requisite for intrathymic production of tumor specific Tregs which supports the role of aire in induction of specifically populated Tregs. Aire’s role in tolerance development is not limited to negative selection but also encompasses Treg induction.

Other Mechanisms:

Aire has a role in induction of apoptosis and absence of this effect results in increased number of MHC class II and mTECs. The aire induced apoptosis facilitates the cross-presentation of TSAs.