PMID- 31539668
OWN - NLM
STAT- MEDLINE
DCOM- 20200121
LR  - 20200121
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 114
DP  - 2019 Oct
TI  - Adhesion between medullary thymic epithelial cells and thymocytes is regulated by 
      miR-181b-5p and miR-30b.
PG  - 600-611
LID - S0161-5890(19)30125-7 [pii]
LID - 10.1016/j.molimm.2019.09.010 [doi]
AB  - 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.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Cotrim-Sousa, Larissa
AU  - Cotrim-Sousa L
AD  - Molecular Immunogenetics Group, Department of Genetics, Ribeirao Preto Medical 
      School, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil.
FAU - Freire-Assis, Amanda
AU  - Freire-Assis A
AD  - Molecular Immunogenetics Group, Department of Genetics, Ribeirao Preto Medical 
      School, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil; State 
      University of Minas Gerais, Passos, MG, Brazil.
FAU - Pezzi, Nicole
AU  - Pezzi N
AD  - Graduate Program in Basic and Applied Immunology, Ribeirao Preto Medical School, 
      University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil.
FAU - Tanaka, Pedro Paranhos
AU  - Tanaka PP
AD  - Molecular Immunogenetics Group, Department of Genetics, Ribeirao Preto Medical 
      School, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil.
FAU - Oliveira, Ernna Herida
AU  - Oliveira EH
AD  - Molecular Immunogenetics Group, Department of Genetics, Ribeirao Preto Medical 
      School, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil.
FAU - Passos, Geraldo Aleixo
AU  - Passos GA
AD  - Molecular Immunogenetics Group, Department of Genetics, Ribeirao Preto Medical 
      School, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil; Graduate 
      Program in Basic and Applied Immunology, Ribeirao Preto Medical School, 
      University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil; Laboratory of Genetics 
      and Molecular Biology, Department of Basic and Oral Biology, School of Dentistry 
      of Ribeirao Preto, USP, Ribeirao Preto, SP, Brazil. Electronic address: 
      passos@usp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190926
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (B7-1 Antigen)
RN  - 0 (Biomarkers)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn30d microRNA, mouse)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Transcription Factors)
RN  - 0 (mirn181 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - B7-1 Antigen/immunology
MH  - Biomarkers/blood
MH  - Cell Adhesion/*immunology
MH  - Cell Differentiation/immunology
MH  - Epithelial Cells/*immunology
MH  - Female
MH  - Gene Expression Regulation/immunology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*immunology
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Self Tolerance/immunology
MH  - Thymocytes/*immunology
MH  - Thymus Gland/*immunology
MH  - Transcription Factors/immunology
OTO - NOTNLM
OT  - Cell adhesion
OT  - Single-positive thymocytes
OT  - Thymus
OT  - mTECs
OT  - miR-181b-5p
OT  - miR-30b*
OT  - miRNA transfection
EDAT- 2019/09/21 06:00
MHDA- 2020/01/22 06:00
CRDT- 2019/09/21 06:00
PHST- 2019/02/12 00:00 [received]
PHST- 2019/09/03 00:00 [revised]
PHST- 2019/09/05 00:00 [accepted]
PHST- 2019/09/21 06:00 [pubmed]
PHST- 2020/01/22 06:00 [medline]
PHST- 2019/09/21 06:00 [entrez]
AID - S0161-5890(19)30125-7 [pii]
AID - 10.1016/j.molimm.2019.09.010 [doi]
PST - ppublish
SO  - Mol Immunol. 2019 Oct;114:600-611. doi: 10.1016/j.molimm.2019.09.010. Epub 2019 
      Sep 26.