The Hidden Pathway: Membrane Vitamin D Receptor Deficiency and T-Cell Senescence in Pediatric Atopic Dermatitis - A Retrospective and Cross-Sectional Investigation.

BACKGROUND

Pediatric Atopic dermatitis (AD) is a common, relapsing inflammatory skin disease in children. While linked to vitamin D deficiency, the roles of T-cell senescence and vitamin D receptor (VDR) signaling remain unclear.

OBJECTIVE

To explore vitamin D status, VDR expression (soluble/sVDR, membrane/mVDR, nuclear/nVDR), and T-cell senescence in pediatric AD.

METHODS

Serum 25-hydroxyvitamin D (25(OH)D) levels were analyzed in 408 pediatric AD patients and matched controls. In a subset (89 patients, 35 controls), plasma sVDR was measured by ELISA. T-cell immunophenotyping, senescence markers (CD27-CD28-), and mVDR/nVDR expression were assessed via flow cytometry.

RESULTS

Children with AD had significantly lower serum 25(OH)D (p<0.05) and sVDR (p<0.05). Although major T-cell subset proportions were similar, children with AD showed expanded senescent populations within CD3⁺ (p<0.01), CD8⁺ (p<0.05), CD4⁺ (p<0.05), and Regulatory T (Treg) cells (p<0.01). mVDR expression was pervasively reduced across all immune cells in pediatric AD (for CD3-, CD3+ and CD8+: p<0.0001; for CD4+, T follicular helper (Tfh) cells: p<0.001; for Treg: p<0.01). Senescent cells expressed higher mVDR than non-senescent cells in both groups (NC: CD3-, p<0.0001; CD3+ and CD8+, p<0.01; CD4+, p<0.001. AD: CD3-, CD3+, CD8+ and CD4+, p<0.0001), yet overall children with AD exhibited lower mVDR levels both in non-senescent and senescent cells (non-senescent cells: CD3-, p<0.001; CD3+ and CD4-, p<0.0001; CD4+, p<0.01. senescent cells:CD3-, CD3+ and CD8+, p<0.0001; CD4+, p<0.01). nVDR alterations were more limited, with elevation only in Tfh cells (p<0.05) of children with AD.

CONCLUSION

Pediatric AD is characterized by accelerated T-cell senescence and a widespread mVDR pathway deficiency. This receptor defect, coupled with vitamin D deficiency, may drive immune dysregulation and premature T-cell aging, highlighting potential therapeutic targets in both ligand and receptor pathways.