LncRNA Malat1 represses Th17 effector program by maintaining a critical bivalent super-enhancer and promotes intestinal inflammation

Ma et al., bioRxiv, 2022 ask what holds interleukin 17A production down in Th17 cells during colitis, and answer that the long non-coding RNA Malat1 does it by sitting on the regulatory elements of the Il17a locus and damping a bivalent super enhancer. Deleting Malat1 in mice raised interleukin 17A from Th17 cells and improved the course of experimental colitis, and Malat1 falls naturally as inflammation resolves.

The AUM material is one experiment inside that story. A single oligonucleotide was made against a specific stretch of Malat1 called region A, alongside a control oligonucleotide of the same chemistry aimed at a Trypanosoma gene so that it has nothing to bind in a mouse cell. Both sequences are printed in the Methods and purity was confirmed by mass spectrometry. They were incubated with activated mouse CD4 T cells for 48 hours following the supplier's instructions, with no transfection reagent described. AUM BioTech is named twice in the Methods.

Treated Th17 cells made more interleukin 17A and more interleukin 17F than cells given the control oligonucleotide, across five independent cultures. The amount of Malat1 itself fell only modestly and the fall did not reach significance, and proliferation as read by Ki67 barely moved. That combination matches the CRISPR result in the same figure, where mutating region A raised the same two cytokines without changing how much Malat1 the cells carried. The authors read both as evidence that region A carries a function of its own rather than acting through the abundance of the transcript. This is a preprint and has not been peer reviewed.