Growing evidence demonstrates that the immunoregulatory properties of vitamin D are primarily mediated by its active hormonal form, 1,25-dihydroxyvitamin D3 (calcitriol). This secosteroid modulates immune homeostasis through three principal mechanisms: (1) strengthening antimicrobial defense via innate immune potentiation, (2) downregulating pathological inflammatory cascades, and (3) fine-tuning adaptive immunity through lymphocyte differentiation control. Clinically, serum concentrations of the inactive precursor, 25-hydroxyvitamin D3 (25(OH)D3), exhibit an inverse correlation with systemic immune activation and the prevalence/severity of dermatological conditions, including atopic dermatitis, psoriasis, and systemic sclerosis. Suboptimal 25(OH)D3 levels are thus recognized as a modifiable risk factor for such disorders, with vitamin D3 supplementation demonstrating therapeutic potential in improving clinical outcomes. Furthermore, prolonged vitamin D3 supplementation may reduce disease incidence across a spectrum of dermatopathologies. This review synthesizes contemporary mechanistic and clinical insights into vitamin D’s immunoregulatory role in cutaneous diseases. To optimize therapeutic efficacy, future clinical trials should incorporate analysis of vitamin D receptor (VDR) polymorphisms as a predictive biomarker in vitamin D3 intervention strategies.

Infections after psychological stress are a major health care problem. Single-cell transcriptomics and lipidomic profiling in a mouse model of stress show that dermal fibroblasts undergoing adipogenesis have defective responses to Staphylococcus aureus skin infection. Adrenalectomy or adrenergic inhibition restores the fibroblast adipogenic response to S. aureus and enables mice to effectively resist infection during stress. Increased susceptibility to S. aureus from stress is attributed to suppression of the antimicrobial peptide cathelicidin ( Camp ) because adrenaline directly inhibits Camp production by fibroblasts, and mice lacking Camp in fibroblasts do not increase infection after stress. Transforming growth factor β (TGFβ) is induced by stress and adrenergic signaling, and inhibition of TGFβ or deletion of the TGFβ receptor on fibroblasts increases Camp expression and restores protection against infection. Together, these data show that stress initiates a brain-skin axis mediated by TGFβ that impairs the immune defense function of dermal fibroblasts to produce the Camp antimicrobial peptide.

Objective: Bifidobacterium is known to be depleted in patients with atopic dermatitis (AD). This study aims to investigate the potential prophylactic effects of Bifidobacterium animalis subsp. lactis BX-BC08 (B. lactis BX-BC08) in a murine model of AD. Design: The immunosuppressive and anti-inflammatory effects of BX-BC08 were evaluated in a MC903-induced AD mouse model. Gut microbiota composition was analyzed by metagenomic sequencing, while high-performance liquid chromatography-mass spectrometry (HPLC-MS) was employed to identify anti-inflammatory molecules produced by B. lactis BX-BC08. Results: BX-BC08 significantly attenuated pro-inflammatory responses, scaling and swelling in the MC903-induced AD like murine model compared to controls. Fecal microbial profiling revealed an enrichment of probiotics and a reduction of pro-inflammatory bacteria in BX-BC08 treated mice. Metabolic analysis of BX-BC08 bacteria culture supernatant and treated mice identified a significant enrichment of alpha-Ketoglutaric acid (AKG). Functional validation in the murine AD model demonstrated that AKG strongly suppressed T helper 2 (Th2)-driven pro-inflammatory responses. Conclusion: BX-BC08 mitigates AD-like inflammation by producing the anti-inflammatory metabolite AKG. BX-BC08 could serve as a novel prophylactic agent for AD prevention.

Mechanisms responsible for delayed wound repair are poorly understood despite the common impact of this disorder on health. To study how Staphylococcus aureus disrupts healing, mouse and human wound repair models were evaluated after exposure to S . aureus or commensal Staphylococcus . Quorum sensing by S . aureus , but not S . hominis , delayed repair and inhibited the expression of genes responsible for lipid metabolism in keratinocytes. S . aureus with inactive accessory gene regulator (agr) did not delay healing, and the inhibition of lipid metabolism was recapitulated in vitro by synthetic phenol soluble modulin α1 (psmα1) and psmα4, genes that are under agr control. However, S . aureus strains with single deletion of psmA , psmB , alpha-hemolysin ( hla ), or hld gene continued to delay repair, suggesting that S . aureus used multiple agr-dependent virulence factors to disrupt healing. These observations provide insight into mechanisms for delayed wound healing, identify quorum sensing as a critical event, and highlight the role of lipid biosynthesis in wound reepithelialization.