The lncRNAs involved in mouse airway allergic inflammation following induced pluripotent stem cell-mesenchymal stem cell treatment.

BACKGROUND

We have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear.

METHODS

Mice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro. Total RNA from the lungs and separated T cells were processed with an lncRNA/mRNA microarray. A series of bioinformatics technologies were used to screen the target lncRNAs.

RESULTS

iPSC-MSCs significantly prevented asthma inflammation and decreased the Th2 cytokine levels. Over 1300 lncRNAs were differentially expressed after the induction of asthma, and 846 or 4176 lncRNAs were differentially expressed with iPSC-MSC treatment in mice or in vitro, respectively. After overlapping the differentially expressed lncRNAs produced in a similar manner in mice and in vitro, 23 lncRNAs and 96 mRNAs were selected, in which 58 protein-coding genes were predicted to be potential targets of the 23 lncRNAs. Furthermore, using a series of bioinformatics technologies, 9 lncRNAs co-expressed with the most differentially expressed mRNAs, which were enriched in terms of the immune response, were screened out via Pearson's correlation coefficient with mRNAs that were involved with inflammatory cytokines and receptors. lncRNAs MM9LINCRNAEXON12105+ and AK089315 were finally emphasized via quantitative real-time PCR validation.

CONCLUSIONS

Our results suggested that aberrant lncRNA profiles were present after asthma induction and iPSC-MSC treatment, suggesting potential targets of allergic inflammation and iPSC-MSC-mediated immunomodulation.