Background/Purpose: The microRNA(miR)29 family is encoded by two separate loci, the miR29ab1 and miR29b2c alleles. We have previously shown that the microRNA(miR)29 family regulates the survival and function of peripheral B cells by analyzing mice with miR29-deficient B cells (B29KO). Furthermore, these B29KO mice develop itching and skin inflammation akin to atopic dermatitis, with a 50% mortality rate. Our investigations using B29KO mice revealed a novel target transcript, Il4ra. This gene encodes the cytokine IL-4 which is an important signaling molecule for immune cell activation and differentiation. In B cells, IL-4 regulates class switch recombination to IgE and affinity maturation in germinal center reactions. We hypothesized that the miR29 family regulates the IL4 signaling cascade in B cells, conferring a susceptibility for developing atopic dermatitis.

Methods: miR-29ab1fl/fl mice (obtained from Dr. Mark Ansel’s lab) and miR-29b2c-/- mice (obtained from Dr. Jining Lu’s Lab) were bred with mb1-cre animals from Jax Labs and maintained on a C57BL/6J background. Littermates without full deletion of miR-29 family of miRNAs were used as controls. We employed flow cytometry, histology, ex vivo stimulation cultures, single-cell RNA sequencing, and statistical analysis software (GraphPad) to analyze data.

Results: We found B29KO B cells have higher expression of Il4ra by both qPCR and single-cell sequencing. Differential gene analysis and pathway enrichment show B29KO mice exhibit heightened IL4 signaling, reduced activation, and negative regulation of cytokine production relative to littermate controls. Ex vivo studies using B cells from B29KO mice revealed an increase in IgE class switching compared with wild-type B cells – a finding recapitulated in B29KO mice that have higher serum IgE titers. When treated with a neutralizing anti-IL4Ra antibody, the phenotype of B29KO mice are rescued from mortality. Interestingly, we found that skin swabs from phenotypic B29KO mice transferred the phenotype to healthy B29KO mice but not littermate controls. Donor and recipient mice were found to be colonized with Staphylococcus aureus and xylosus.

Conclusion: Our data suggest that regulation of Il4ra by miR-29 impacts B cells responsiveness to IL-4 signaling and, as a result, the susceptibility to atopic dermatitis in mice via genetic susceptibility and microbial triggers.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/loss-of-microrna29-expression-in-b-cells-and-skin-microbiota-synergize-to-promote-atopic-dermatitis-in-mice/