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 Nfatc1f/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, Nfatc1f/fxmb1cre 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.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-11247-9.

IntroductionSkeletal muscle satellite cells (MuSCs or stem cells) play a crucial role in muscle development, maintenance, and regeneration, supporting both hypertrophy and regenerative myogenesis. Syndecans (SDCs) act as communication bridges within the muscle microenvironment, regulating interactions with extracellular matrix components and contributing significantly to tissue repair and inflammation. Specifically, syndecan-4 (SDC4) is involved in muscle regeneration at multiple stages.MethodsThis study delves into the emerging challenge of wooden breast (WB) myopathy and its connection with SDC4. Our hypothesis proposes that disruptions in MuSC dynamics through SDC4 contribute to the increased incidence of breast myopathies observed in growing broilers. To test our hypothesis, non-affected and affected broilers were systematically selected, and the characteristics of WB myopathy were studied both in vitro and in vivo. SDC4 overexpression in MuSCs and blocking peptides (BPs) corresponding to the SDC4 ectodomain were used for investigating the role of SDC4 in muscle development and its shedding levels.Results and discussion In vivo examination of affected muscles revealed smaller fibers and changes in metabolic pathways. In vitro studies unveiled disrupted proliferation of MuSCs in WB myopathy, accompanied by the downregulation of several muscle markers. Investigation of the potential role of SDC4 in the pathogenesis of WB myopathy revealed a decreased tendency in SDC4 gene expression and increased shedding of its ectodomain. Moreover, we showed that SDC4 overexpression is linked to reduced proliferation in MuSCs and affected myogenesis. We detected an impaired proliferation of WB-affected MuSCs, revealing critical insights into the dysfunctional state of these cells in myopathy. Additionally, by treating MuSCs with blocking peptides derived from the SDC4 ectodomain, we identified altered proliferation. Taken together, this work contributes with valuable knowledge on the molecular mechanisms underlying WB myopathy and the role of SDC4 in this chicken myopathy.

The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool. The role of Lgr5+ cells in esophageal development has been unclear. Here, authors identify Lgr5+ cells in the developing mouse esophagus and reveal their crucial role in epithelial and muscle development.