Recently, the journal Nature Communications published two studies regarding microRNA-31 simultaneously, the corresponding author of which is Professor Honglin Wang, a principle investigator from Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine. These two articles reveal a dynamic role of miR-31 in the development of multiple sclerosis and psoriasis, as well as the underlying molecular mechanisms, which leads to a better understanding of the therapeutic strategy of autoimmune diseases.

Autoimmune diseases are generally caused by the immune response from immune system to the body’s own organs, resulting in tissue damage and dysfunction. Currently, autoimmune diseases affect 5-7% of the global population. Particularly, multiple sclerosis and psoriasis become research hot spots due to high lethality or recurrence and the need for long-term medication. MicroRNAs are short non-coding RNAs targeting message RNAs to repress gene expression thus exerting post-transcriptional regulation. Recent researches identify abnormal expression profiles of microRNAs in autoimmune diseases, suggesting that these small RNAs might be involved in the onset and ongoing of the diseases.

Lingyun Zhang, a PhD student supervised by Professor Wang, identified that mice lacking miR-31 in CD4⁺ T cells developed alleviated EAE due to increased generation of peripheral regulatory T cells. Further investigation reveals that miR-31 targets the 3’ UTR of a G-protein coupled receptor named Gprc5a to serve a function. With the in vivo analyses of Gprc5a^-/- mice, the researchers found that the ability of naïve CD4⁺ T cells to differentiate into peripheral-induced Treg cells was impaired in the absence of Gprc5a, which lead to exacerbated phenotype of EAE. Thus, they conclude that miR-31 negatively regulates peripheral Treg cell generation by repressing Gprc5a. These findings uncover a novel mechanism for the epigenetic regulation of Treg cell generation, offering new therapeutic targets to autoimmune diseases including multiple sclerosis.

Sha Yan, Zhenyao Xu and Fangzhou Lou performed the other research directed by Professor Wang on psoriasis. They report that the NF-kB activation triggered by inflammatory cytokines induces the transcription of miR-31, one of the most dynamic microRNAs identified in the skin of psoriatic patients and mouse models. Moreover, protein phosphatase 6, a negative regulator that restricts G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. Genetic deficiency of miR-31 in keratinocytes inhibits their hyperproliferation, decreases acanthosis and reduces the disease severity in psoriasis mouse models. Hence, miR-31 might also be a potential therapeutic target in psoriasis.

These two works were supported by grants from 973 program and National Natural Science Foundation of China (No. 2012CB917100, No. 2014CB541905, No. 31330026, and No. 91029730).

(by Sha Yan)