MicroRNA-29 regulates IgE class-switching in B cells and susceptibility to skin inflammation

• Published in: The Journal of immunology (1950) Vol. 212; no. 1_Supplement; pp. 1024 - 1024_6084
• Main Authors: Borbet, Timothy, Hines, Marcus, Boehringer, Thomas, Morrison, Tate, Gonzalez, Sandra, Koralov, Sergei
• Format: Journal Article
• Language: English
• Published: 01-05-2024
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.212.supp.1024.6084

MicroRNA (miRNA) gene regulation is vital for the development of B cells. Our group established that the miR-29 family is a regulator of B cell survival and B cell receptor (BCR) signaling. Specifically, we identified PTEN as a direct target of miR-29. Conditional knockout of miR-29 in B cells diminishes cell viability, which is compensated by normalizing Pten expression. In our latest observations, mice with a B-cell-specific miR-29 deletion exhibited an inflammatory skin phenotype, characterized by cutaneous lesions, continuous itching and a 50% survival rate. Pten ablation fails to improve their lifespan. These findings indicate that miR-29 targets other transcripts in B cells apart from Pten. Notable features such as epidermal proliferation and elevated serum IgE levels. We hypothesize the absence of miR-29 in B cells may lead to to atopic dermatitis. Computational analysis predicts miR-29 likely regulates Il4Ra transcript levels, and qPCR supports this prediction. Our in vitro assays demonstrate that B cells deficient in miR-29 exhibit greater IgE class switching when stimulated with IL-4, compared to wild-type counterparts. Additionally, we observed that mice developing inflammatory skin conditions harbor an increased Staphylococcus burden. Therefore, we propose that miR-29 plays a role in the co-regulation of Pten and Il4ra to influence the survival and function of mature B cells and may alter how these cells respond to environmental/microbial antigens.