NFATc1 deficiency in B cells ameliorates atopic dermatitis.

Atopic dermatitis (AD) is a common skin allergy, affecting large population worldwide. Currently, there is no cure for AD. NFATc1, a transcription factor, operates through a calcium-dependent calcineurin/calmodulin pathway to regulate target genes and is vital in immune system development and function. Previous research suggests that NFATc1 suppresses IL-10 in B cells by binding to its gene. Our current study explores the role of B cells deficient of NFATc1 during calcipotriol, a vitamin D analog, induced AD responses. Our data showed that Nfatc1(f/f) x mb1cre AD mice exhibited a diminished AD phenotype compared with WT AD mice, by reduced ear swelling, lower epidermal thickening, and fewer cellular infiltration to ear. This was evident by unaltered IgE levels. Interestingly, Nfatc1(f/f)xmb1cre AD mice displayed a higher percentage of IL-10-producing B220(+)CD5(+)CD1d(+) Breg cells, indicating that NFATc1 deficiency promotes the differentiation of B cells into Bregs that produce more anti-inflammatory IL-10, thus alleviating AD symptoms. At the transcriptome level, NFATc1 deficient B cells bearing AD mice exhibited distinct gene expression profiles compared with WT AD mice, with genes that promoted B-cell development and enhanced stress and stimulus responses. This study highlights the potential of targeting NFATc1 as a molecular strategy to reduce AD symptoms without impairing B-cell function while boosting the production of the endogenous anti-inflammatory IL-10.