Authors
Adriana Arruda Matos, Itauá Leston Araujo, Matheus Dominato Munuera, Patrícia Viana Bonini Palma, Camila Bonaldo, Letícia Agrelli Brito, Daniella Arêas Mendes-da-Cruz, Wilson Savino, Geraldo Aleixo Passos, Eduardo Antônio Donadi
Published in
Immunology letters. Pages 107238. Sep 06, 2026. Epub Sep 06, 2026.
Abstract
The autoimmune regulator (Aire) gene is essential for the establishment of central tolerance by promoting the ectopic expression of tissue-restricted antigens in medullary thymic epithelial cells (mTECs). Although Aire deficiency impairs negative selection, its impact on thymic architecture, output, and early T cell development remains incompletely understood. Here, we used a murine Aire-deficient model carrying a CRISPR-Cas9-induced deletion within exon 6, disrupting the SAND domain, to investigate the consequences of Aire loss on thymic structure and function. Aire-deficient mice exhibited focal alopecia and marked disorganization of the thymic medulla. T cell receptor excision circle (TREC) analyses revealed altered peripheral TREC dynamics and a reduced sj/betaTREC ratio, indicating altered thymic output and impaired intrathymic precursor expansion. Complementary flow-cytometric analysis showed a significant reduction in the proportion of CD4+CD8+ double-positive thymocytes in heterozygous mutants, supporting altered intrathymic maturation. Serum IL-27, IL-28B, and IL-31 were decreased in homozygous mutants, whereas IL-22 and IL-23 remained unchanged. Despite these alterations, TCRVbeta repertoire sequencing revealed no significant differences in rearrangements, clonality, or V/J gene usage. Together, these findings indicate that Aire deficiency disrupts thymic architecture and output, while preserving overall TCR repertoire diversity.
PMID:
42702337
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.
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