An international team of researchers including scientists from The Scripps Research Institute (TSRI) believes their work has opened a new door  to influencing the immune system, which would be useful to boost the effectiveness of vaccines or to counter autoimmune diseases such as lupus and rheumatoid arthritis.


Their 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, focused on microRNA-155 (miR-155), a key player in the immune system's production of disease-fighting antibodies. 


“It's very exciting to see exactly how this molecule works in the body,” said TSRI Associate Professor Changchun Xiao, Ph.D., who co-led the study with Professor Wen-Hsien Liu, Ph.D., of Xiamen University in Fuijan province, China.


microRNAs (miRNAs) serve as a sort of “dimmer switches” to regulate protein levels carefully and combat disease.


“People know miRNAs are involved in immune response, but they don't know which miRNAs and how exactly,” explained TSRI Research Associate Zhe Huang, study co-first author with Liu and Seung Goo Kang of TSRI and Kangwon National University.


In the new study, the researchers focused on the roles of miRNAs during the critical period when the immune system first detects as viruses or bacteria. At this time, T follicular helper cells proliferate and migrate to a different area of the lymph organs to interact with B cells.


“They do a sort of tango,” said Dr. Xiao.


This interaction prompts B cells to mature and produce effective antibodies, eventually offering long-term protection against infection.


Using deep sequencing, the team identified miR-155 as a potential part of this process. Studies in mouse models suggested that miR-155 works by repressing a protein called Peli1. This leaves a molecule called c-Rel free to jump in and promote normal T-cell proliferation.


This finding could help scientists improve current vaccines. While vaccines are life-saving, some vaccines wear off after a decade or only cover around 80% of 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%,” said Dr. Xiao. He also sees potential for using miR-155 to help in creating longer-lasting vaccines.


The research may also apply to treating autoimmune diseases, which occur when antibodies mistakenly attack the body's own tissues. Dr. Xiao and his colleagues think an mRNA inhibitor could dial back miR-155's response when T-cell proliferation and antibody production is in overdrive.


For the next stage of this research, Dr. Xiao plans to collaborate with scientists on the Florida campus of TSRI to test possible miRNA inhibitors against autoimmune disease.