Effect of lymphotoxin beta receptor blockade on microRNA expression in the spleen
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Neil Mabbott
PROVIDER: E-GEOD-55722 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
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.
Aungier Susan R SR Ohmori Hitoshi H Clinton Michael M Mabbott Neil A NA
Immunology 20150101 1
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 tr ...[more]
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Project description: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 which they display to B cells, in order to select those cells with the highest antigen affinity. MicroRNAs are short, non-coding RNAs of 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 are differentially expressed as a result of FDC depletion. Constitutive lymphotoxin-M-NM-2 receptor (LTM-NM-2R) stimulation is required to maintain FDC in their differentiated state. We show that the rapid de-differentiation of spleen FDC that followed LTM-NM-2R-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 in this cell line. The expression of each of these genes by FDC plays an important role in regulating GC size and promoting high-affinity antibody responses, suggesting that mmu-miR-100-5p may help regulate their expression during GC reactions. C57BL/6 mice were given a single intravenous injection of 100 M-BM-5g of LTM-NM-2R to temporarily deplete their FDC. At intervals after treatment 4 spleens from each group were harvested and RNA prepared. For each group samples were pooled into 2 groups of 2 and microRNA expression levels compared. Spleens from LTb-/- mice were also analysed. One channel was used for the actual sample, the second channel was used for internal QC reference.
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