The absence of the autoimmune regulator gene (AIRE) impairs the three‑dimensional structure of medullary thymic epithelial cell spheroids
Carregando...
Data
Data de publicação
Autores IPEN
Orientador
Título da Revista
ISSN da Revista
Título do Volume
É parte de
É parte de
É parte de
BMC Molecular and Cell Biology
Exportar
Resumo
Background: Besides controlling the expression of peripheral tissue antigens, the autoimmune regulator (AIRE) gene
also regulates the expression of adhesion genes in medullary thymic epithelial cells (mTECs), an essential process
for mTEC-thymocyte interaction for triggering the negative selection in the thymus. For these processes to occur, it
is necessary that the medulla compartment forms an adequate three-dimensional (3D) architecture, preserving the
thymic medulla. Previous studies have shown that AIRE knockout (KO) mice have a small and disorganized thymic
medulla; however, whether AIRE influences the mTEC-mTEC interaction in the maintenance of the 3D structure has
been little explored. Considering that AIRE controls cell adhesion genes, we hypothesized that this gene affects 3D
mTEC-mTEC interaction. To test this, we constructed an in vitro model system for mTEC spheroid formation, in which
cells adhere to each other, establishing a 3D structure.
Results: The comparisons between AIRE wild type (AIREWT) and AIRE KO (AIRE−/−) 3D mTEC spheroid formation
showed that the absence of AIRE: i) disorganizes the 3D structure of mTEC spheroids, ii) increases the proportion of
cells at the G0/G1 phase of the cell cycle, iii) increases the rate of mTEC apoptosis, iv) decreases the strength of mTECmTEC
adhesion, v) promotes a differential regulation of mTEC classical surface markers, and vi) modulates genes
encoding adhesion and other molecules.
Conclusions: Overall, the results show that AIRE influences the 3D structuring of mTECs when these cells begin the
spheroid formation through controlling cell adhesion genes.
Como referenciar
MONTELEONE-CASSIANO, ANA C.; DERNOWSEK, JANAINA A.; MASCARENHAS, ROMARIO S.; ASSIS, AMANDA F.; PITOL, DIMITRIUS; MOREIRA, NATALIA C.S.; SAKAMOTO-HOJO, ELZA T.; ISSA, JOAO P.M.; DONADI, EDUARDO A.; PASSOS, GERALDO A. The absence of the autoimmune regulator gene (AIRE) impairs the three‑dimensional structure of medullary thymic epithelial cell spheroids. BMC Molecular and Cell Biology, v. 23, n. 1, p. 1-17, 2022. DOI: 10.1186/s12860-022-00414-9. Disponível em: http://repositorio.ipen.br/handle/123456789/33159. Acesso em: 27 Mar 2026.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.