Adhesion between medullary thymic epithelial cells and thymocytes is regulated by miR-181b-5p and miR-30b

Autor(es)

Cotrim-Sousa, Larissa ^[1] ; Freire-Assis, Amanda ^{[1, 2]} ; Pezzi, Nicole ^[3] ; Tanaka, Pedro Paranhos ^[1] ; Oliveira, Ernna Herida ^[1] ; Passos, Geraldo Aleixo ^{[3, 1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Mol Immunogenet Grp, Via Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Estado Minas Gerais, Passos, MG - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Grad Program Basic & Appl Immunol, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Lab Genet & Mol Biol, Dept Basic & Oral Biol, Sch Dent Ribeirao Preto, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Immunology; v. 114, p. 600-611, OCT 2019.
• Citações Web of Science: 1

Resumo

In this work, we demonstrate that adhesion between medullary thymic epithelial cells (mTECs) and thymocytes is controlled by miRNAs. Adhesion between mTECs and developing thymocytes is essential for triggering negative selection (NS) of autoreactive thymocytes that occurs in the thymus. Immune recognition is mediated by the MHC / TCR receptor, whereas adhesion molecules hold cell-cell interaction stability. Indeed, these processes must be finely controlled, if it is not, it may lead to aggressive autoimmunity. Conversely, the precise molecular genetic control of mTEC-thymocyte adhesion is largely unclear. Here, we asked whether miRNAs would be controlling this process through the posttranscriptional regulation of mRNAs that encode adhesion molecules. For this, we used small interfering RNA to knockdown (KD) Dicer mRNA in vitro in a murine mTEC line. A functional assay with fresh murine thymocytes co-cultured with mTECs showed that single-positive (SP) CD4 and CD8 thymocyte adhesion was increased after Dicer KD and most adherent subtype was CD8 SP cells. Analysis of broad mTEC transcriptional expression showed that Dicer KD led to the modulation of 114 miRNAs and 422 mRNAs, including those encoding cell adhesion or extracellular matrix proteins, such as LgaLs9, Lgals3pb, Tnc and Cd47. Analysis of miRNA-mRNA networks followed by miRNA mimic transfection showed that these mRNAs are under the control of miR-181b-5p and miR-30b{*}, which may ultimately control mTEC-thymocyte adhesion. The expression of CD80 surface marker in mTECs was increased after Dicer KD following thymocyte adhesion. This indicates the existence of new mechanisms in mTECs that involve the synergistic action of thymocyte adhesion and regulatory miRNAs. (AU)

• Processo FAPESP: 13/17481-1 - A função do gene AIRE e de micro RNAs no controle da adesão de células tímicas epiteliais medulares com timócitos
• Beneficiário: Geraldo Aleixo da Silva Passos Júnior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/10780-4 - Efeito de mutações no gene AIRE (síndrome APS1) induzidas por CRISPR-Cas9 na conformação da proteína, no transcriptoma de células mTEC e na sua interação com timócitos
• Beneficiário: Geraldo Aleixo da Silva Passos Júnior
• Modalidade de apoio: Auxílio à Pesquisa - Temático