MicroRNA May Offer Way to Control T-cells in RA and Other Autoimmune Diseases

MicroRNA May Offer Way to Control T-cells in RA and Other Autoimmune Diseases

An international collaboration involving researchers at The Scripps Research Institute (TSRI) unveiled the role a small molecule called microRNA-155 (miR-155) plays in our immune system, a finding that could help scientists develop novel therapies for autoimmune diseases, such as rheumatoid arthritis and lupus, and, possibly, longer-lasting vaccines.

The study, “A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells,” was published in the Journal of Experimental Medicine (JEM).

MicroRNAs are small RNA molecules that play key roles in regulating the expression of our genome by dictating the levels of expression of all proteins within our body.

Previous studies have shown that deleting a key component of microRNAs’ machinery in specific immune cells, called T-cells, severely impairs the generation of a subtype of these immune players, the T follicular helper cells. However, how individual microRNAs contributed to this phenotype remain unknown.

“People know miRNAs are involved in immune response, but they don’t know which miRNAs and how exactly,” Zhe Huang, a study author, said in a press release.

The team investigated the different roles of miRNAs when the immune system first encounters signs of danger, such as viruses or bacteria, particularly focusing on T follicular helper cells that interact with B -cells, the cells responsible for generating antibodies against specific antigens, and in promoting the clearing of infections.

“They do a sort of tango,” said Changchun Xiao, a study co-leader and TSRI associate professor. Interaction with T follicular helper cells promotes the maturation of B-cells and their effective production of antibodies, so that “the next time you encounter that virus, for example, the body can respond quickly,” Xiao said.

The team identified a specific miRNA, miR-155, as a potential part of this process. Studies in mice genetically engineered to lack miR-155 revealed that it works by repressing the expression of a protein called Peli1. This, in turn, leaves a molecule called c-Rel free to induce normal T-cell proliferation and produce a specific ligand, called CD40L, that is essential for T follicular helper and B-cell interaction.

This finding  could lead to the development of miR-155 inhibitors of use in the setting of autoimmune diseases, where T-cell proliferation and antibody production are excessive.

It also suggests that miR-155 is a potential target for creating longer-lasting vaccines. Some vaccines’ protective properties wear off every 10 years or so, and some are only effective in about 80 percent of all those vaccinated.

“If you could increase T cell proliferation using a molecule that mimics miR-155, maybe you could boost that to 90 to 95 percent,” Xiao said.

 

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