Narrowband Ultraviolet B Induces Peripheral Regulatory T Cells to Exert Antigen‐Specific Immune Suppression

Background Commonly used to treat inflammatory skin diseases, narrowband ultraviolet B (UVB) has been shown to induce antigen‐specific immune suppression when combined with alloantigen immunization, but the underlying mechanism remains elusive. Methods We used cytometry by time‐of‐flight (CyTOF) to analyze the peripheral blood mononuclear cells (PBMCs) from 19 psoriasis patients enrolled in UVB trial. Mouse models of ovalbumin (OVA)‐induced skin inflammation and allogeneic skin transplantation were used to investigate the effects of UVB on antigen‐specific regulatory T cell (Treg) induction. We applied bulk RNA sequencing (RNA‐seq) and single‐cell RNA sequencing (scRNA‐seq) methods to the analyses of mouse skin Tregs and PBMCs, respectively. Results CyTOF analysis revealed patients’ therapeutic response to be determined by a cluster of CD4 + T cells expressing T cell receptor (TCR)‐activated and Treg‐associated molecules. In clinical trial and mouse models of skin inflammation and allogeneic skin transplantation, UVB led to immunosuppressive phenotypes through antigen‐specific Treg induction. RNA‐seq from mouse skin Tregs showed that UVB enhanced gene expression associated with cell stability, cellular location, and cell proliferation. When compiling with human peripheral Tregs analyzed by scRNA‐seq, we found similar gene expression patterns involved in Treg differentiation, maintenance, and function. Furthermore, scRNA‐seq analysis also demonstrated that UVB inhibited negative regulators of Treg development, thereby promoting CD4 + T differentiation into Tregs, clonal expansion of which was also noted. Conclusions Our findings suggest UVB can induce antigen‐specific Tregs in a clinical setting, highlighting its potential for broader immunosuppressive applications.