Research into MicroRNA May Lead to New Lupus Therapy, Better Vaccines

Research into MicroRNA May Lead to New Lupus Therapy, Better Vaccines
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New research into a microRNA that helps to produce antibodies offering long-term protection against disease takes science a step close to finding a way to boost vaccine responses, and possibly to understanding how the molecule might be used to counter the development of autoimmune diseases like lupus.

The study, “A miR-155–Peli1–c-Rel pathway controls the generation and function of T follicular helper cells,” published in The Journal of Experimental Medicine, describes the role of the microRNA, called miR-155, in the production of antigen-specific antibodies required for long-term immunity.

When the body first detects pathogens, such as virus or bacteria, a sequential process that ultimately leads to the generation of antibody-producing B-cells (against foreign pathogens) is initiated. This process involves the proliferation of immune cells, called T follicular helper (Tfh) cells, and their migration to a specific site on the lymph nodes, where they interact with B-cells.

“They do a sort of tango,” the study’s co-lead author, Professor Changchun Xiao of the Scripts Research Institute (TSRI), said in a press release.

This interaction induces B-cell maturation and promotes the expression of highly specific antibodies against the “invaders,” eventually leading to long-term protection against infection by these pathogens.

Researchers were interested in understanding the molecular mechanisms that led to Tfh differentiation and function during the first contact with a specific pathogen. Their interest was based on evidence showing that these cells are essential to controlling chronic virus infection, and that high levels of Tfh can lead to autoimmunity.

Because a number of studies have shown that microRNAs, small DNA molecules that control gene expression, are critical regulators of Tfh and B-cell interaction, scientists focused their attention on Tfh-derived microRNAs.

“People know miRNAs are involved in immune response, but they don’t know which miRNAs and how exactly,” said Zhe Huang, a TSRI research associate and the study’s co-first author.

Through a technique that quantifies gene expression, called deep sequencing, the researchers identified miR-155 as a key player in this process. Studies in mice genetically engineered to lack miR-155 revealed it represses 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 Tfh and B-cell interaction.

The researchers believe that their findings may help increase the efficacy and durability of vaccines. A number of vaccines lose their effectiveness after a decade, and some are only effective in 80 percent of the people 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,” said Xiao.

In addition, the findings may also lead to the development of miR-155 inhibitors that could be useful in the setting of autoimmune diseases, where T-cell proliferation and antibody production are excessive.

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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