Red-Blue Light Therapy Mitigates Atopic Dermatitis via CD56bright NK Cell Modulation: A Mendelian Randomization Study

This study investigates the role of the CD56bright NK cell subpopulation, cytokine levels, and the effectiveness of red-blue light therapy in elderly patients with Atopic Dermatitis (AD) using Mendelian Randomization (MR) analysis, aiming to uncover molecular mechanisms behind phototherapy in elderly AD.

MR analysis utilized genetic variants as instrumental variables to assess the causal relationship between NK cell subtypes and AD. AD single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database was analyzed for NK cell feature genes, followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A protein-protein interaction (PPI) network was constructed to identify key genes implicated in AD. Peripheral Blood Mononuclear Cells (PBMCs) from AD mouse models were isolated for flow cytometry to analyze NKreg cell subpopulations post red-blue light exposure, assess NKreg-mediated K562 cell lysis, and measure inflammatory cytokines via ELISA and qPCR. The expression of the critical factor NKG2D was knocked down to investigate its effects. This was validated in AD mouse models by measuring changes in NKreg cell subpopulations, cytokine levels, and skin lesion severity after red-blue light exposure.

MR analysis revealed no significant genetic association between Terminal NK cells and AD. However, an increased number of CD56bright NK cells may exert a protective effect by reducing AD risk. scRNA-seq analysis identified eight cell types, including NK cells. GO/KEGG and PPI analyses pinpointed NKG2D as a key gene in the NK cell cytotoxic pathway. In AD mouse models, red-blue light exposure significantly increased CD56bright NK cell count and enhanced anti-inflammatory activity, alleviating AD severity.

MR analysis confirmed the genetic association between CD56bright NK cells and AD, whereas scRNA-seq analysis highlighted their potential to inhibit AD progression. In vitro and in vivo experiments showed that red-blue light therapy promotes CD56bright NK cell growth by upregulating NKG2D, significantly improving AD symptoms.