Passos · Advances in experimental medicine and biology 2025 · narrative review · n=?

The Thymus as a Mirror of the Body's Gene Expression.

Level 5 - mechanism / opinion, no new human data

Narrative review of mechanistic and preclinical concepts without new empirical human data

PubMed 40067590 · doi:10.1007/978-3-031-77921-3_9 · record verified 2026-08-26

What was done

This is a narrative review chapter summarizing the molecular mechanisms of promiscuous gene expression (PGE) in medullary thymic epithelial cells (mTECs). It reviews the interaction between stromal thymic epithelial cells and developing thymocytes, the regulation of peripheral tissue antigens (PTAs) by AIRE/Aire and FEZF2/Fezf2, the influence of Aire on microRNA expression in mTECs, and experimental manipulation of Aire using siRNA and CRISPR-Cas9 genome editing.

What was found

The abstract reports no numerical findings or statistical measures. It conceptually summarizes that mTECs transcribe a broad set of the functional genome to present PTAs, which facilitates self-nonself discrimination and elimination of autoreactive thymocytes via negative selection under the control of Aire and Fezf2.

Why it matters

Elucidating the genetic and transcriptional controls of promiscuous gene expression in the thymus clarifies the foundational biology of central immune tolerance and the origins of autoimmune disease.

Limits

This is a narrative review chapter with no systematic search criteria, human clinical trial data, or quantitative metrics reported in the abstract. The underlying evidence primarily relies on basic bench and animal models.