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Extrathymic AIRE-Expressing Cells: A Historical Perspective.

Dominik Filipp¹, Jasper Manning², Jana Petrusová²

¹Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic. dominik.filipp@img.cas.cz.

Advances in Experimental Medicine and Biology

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Summary

Aire

Keywords:

AIRE Fertility Immune periphery Non-immune function RORγt+ eTACs Sertoli cells Th17 responses Transcription function eTACs mTECs

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Area of Science:

Immunology
Molecular Biology
Genetics

Background:

Aire is a transcriptional regulator in the thymus, crucial for preventing autoimmunity by controlling self-antigen expression.
Extrathymic Aire expression in peripheral organs is a recent area of intense research.
Understanding extrathymic Aire's cellular sources and functions is key to its broader physiological roles.

Purpose of the Study:

To analyze the progression of extrathymic Aire research.
To identify cellular sources and mechanisms of extrathymic Aire.
To determine the function of extrathymic Aire in peripheral tissues.

Main Methods:

Review of recent studies on extrathymic Aire.
Analysis of OMICs tools, including single-cell RNA sequencing.
Examination of novel transgenic models for lineage tracing.

Main Results:

Extrathymic Aire has functions distinct from its thymic role, primarily regulating cell-specific transcriptional programs.
Evidence suggests a non-transcriptional, cytoplasmic role for extrathymic Aire.
Aire's function extends beyond transcription factor activity in the periphery.

Conclusions:

Extrathymic Aire plays diverse roles in immunological and non-immunological processes.
Aire's function is context-dependent, varying between thymic and peripheral tissues.
Future research will redefine Aire's role beyond central tolerance induction.