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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Aire knockdown in medullary thymic epithelial cells affects Aire protein, deregulates cell adhesion genes and decreases thymocyte interaction

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Pezzi, Nicole ; Assis, Amanda Freire ; Cotrim-Sousa, Larissa Cotrim ; Lopes, Gabriel Sarti ; Mosella, Maritza Salas ; Lima, Djalma Sousa ; Bombonato-Prado, Karina F. ; Passos, Geraldo Aleixo
Total Authors: 8
Document type: Journal article
Source: Molecular Immunology; v. 77, p. 157-173, SEP 2016.
Web of Science Citations: 5

We demonstrate that even a partial reduction of Aire mRNA levels by siRNA-induced Aire knockdown (Aire KD) has important consequences to medullary thymic epithelial cells (mTECs). Aire knockdown is sufficient to reduce Aire protein levels, impair its nuclear location, and cause an imbalance in large-scale gene expression, including genes that encode cell adhesion molecules. These genes drew our attention because adhesion molecules are implicated in the process of mTEC-thymocyte adhesion, which is critical for T cell development and the establishment of central self-tolerance. Accordingly, we consider the following: 1) mTECs contribute to the elimination of self-reactive thymocytes through adhesion; 2) Adhesion molecules play a crucial role during physical contact between these cells; and 3) Aire is an important transcriptional regulator in mTECs. However, its role in controlling mTEC-thymocyte adhesion remains unclear. Because Aire controls adhesion molecule genes, we hypothesized that the disruption of its expression could influence mTEC-thymocyte interaction. To test this hypothesis, we used a murine Aire mTEC cell line as a model system to reproduce mTEC-thymocyte adhesion in vitro. Transcriptome analysis of the mTEC cell line revealed that Aire KD led to the down-modulation of more than 800 genes, including those encoding for proteins involved in cell adhesion, i.e., the extracellular matrix constituent Lama1, the CAM family adhesion molecules Vcam1 and Icam4, and those that encode peripheral tissue antigens. Thymocytes co-cultured with Aire KD mTECs had a significantly reduced capacity to adhere to these cells. This finding is the first direct evidence thatAire also plays a role in controlling mTEC-thymocyte adhesion. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 13/17481-1 - The function of the AIRE gene and of Micro RNAs in the control of adhesion between medullary thymic epithelial cells with thymocytes
Grantee:Geraldo Aleixo da Silva Passos Júnior
Support type: Regular Research Grants