MicroRNA-100-5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA in the mouse follicular dendritic cell-like cell line, FL-Y

Immunology. 2015 Jan;144(1):34-44. doi: 10.1111/imm.12342.

Abstract

Follicular dendritic cells (FDC) are important stromal cells within the B-cell follicles and germinal centres (GC) of secondary lymphoid tissues. FDC trap and retain native antigens on their surfaces in the form of immune complexes that they display to B cells, in order to select those cells with the highest antigen affinity. MicroRNAs are short, non-coding RNAs that are approximately 18-25 nucleotides in length that regulate gene expression at the post-transcriptional level by repressing the translation of target genes. In the current study, in vivo and in vitro systems were used to identify microRNAs that were potentially expressed by FDC. Constitutive lymphotoxin-β receptor (LTβR) stimulation is required to maintain FDC in their differentiated state. We show that the rapid de-differentiation of spleen FDC that accompanied LTβR-blockade, coincided with a significant decrease in the expression of mmu-miR-100-5p, mmu-miR-138-5p and mmu-miR-2137. These microRNAs were shown to be expressed in the FDC-like cell line, FL-YB, and specific inhibition of mmu-miR-100-5p significantly enhanced expression of Il6, Ptgs1/2 and Tlr4 mRNA in this cell line. The expression of Il6, Ptgs1/2 and Tlr4 by FDC play important roles in regulating GC size and promoting high-affinity antibody responses, so it is plausible that mmu-miR-100-5p may help to regulate the expression of these genes during GC reactions.

Keywords: follicular dendritic cell; mRNA; microRNA; mmu-miR-100-5p; spleen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / immunology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / immunology*
  • Dendritic Cells, Follicular / cytology
  • Dendritic Cells, Follicular / immunology*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Lymphotoxin beta Receptor / genetics
  • Lymphotoxin beta Receptor / immunology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*

Substances

  • Interleukin-6
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Membrane Proteins
  • MicroRNAs
  • Mirn100 microRNA, mouse
  • RNA, Messenger
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Ptgs2 protein, mouse
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Ptgs1 protein, mouse