ZKKL Academic Sharing | The Effects of Narrowband UVB Therapy on Cutaneous Immune Cells and Cytokines

This article is reprinted from: Chinese Journal of Dermatology and Venereology.

Author: Jiang Xiaoxia

[Abstract] Narrowband UVB (NB-UVB) is effective in the treatment of certain skin diseases, but its underlying mechanisms remain unclear. Studies have shown that NB-UVB can reduce the number of immune cells and suppress cytokine production, thereby achieving therapeutic effects in specific dermatologic conditions. This review summarizes the roles of NB-UVB in modulating immune cell function and cytokine expression in the management of common skin disorders.

[Keywords] NB-UVB; immune cells; cytokines

Ultraviolet irradiation is widely used in dermatological practice, and the biological effects of ultraviolet light vary with wavelength. Narrow-band ultraviolet B (NB‑UVB), with wavelengths between 311 and 313 nm, exhibits strong skin penetration, a relatively mild erythematous response, and a low risk of skin burns or DNA mutations. Consequently, it is extensively employed in the clinical management of refractory skin disorders such as psoriasis, vitiligo, atopic dermatitis, cutaneous T‑cell lymphoma, pruritus, lichen planus, and seborrheic dermatitis. To date, it remains unclear whether NB‑UVB exerts primarily local effects or systemic actions. Existing studies indicate that NB‑UVB can effectively reduce the numbers of immune cells, including T cells and dendritic cells, and suppress cytokine production, thereby mediating therapeutic benefits in skin diseases. This review summarizes how NB‑UVB modulates the expression of cutaneous immune cells and cytokines to facilitate the treatment of various skin conditions.

1. The effects of NB-UVB on cutaneous T lymphocytes

Although the etiology of certain skin diseases, such as vitiligo and psoriasis, remains unclear, they are closely linked to immune mechanisms, with T lymphocytes playing a key role in their pathogenesis. Both animal studies and clinical trials have demonstrated that the activation of CD4+ and CD8+ T cells is essential for the onset and progression of immune‑mediated skin disorders, and that this process requires interaction with dendritic cells. The therapeutic effects of most NB‑UVB treatments on skin diseases are likely attributable to their immunosuppressive properties. Experimental evidence indicates that NB‑UVB at an irradiance of 0.28–2 J/cm², administered three times per week systemically, can effectively suppress the activation of CD4+ helper T cells in patients with vitiligo while enhancing the activity of regulatory T cells, thereby promoting patient recovery. Moreover, combining twice‑weekly NB‑UVB exposure with topical application of 0.1% tacrolimus yields even more robust outcomes in the treatment of segmental vitiligo. Comparative studies have further shown that UVB at 312 nm, with an energy dose of 50–100 mJ/cm², induces greater apoptosis of T cells within psoriatic plaques than UVB in the 290–320 nm range, leading to significant improvements in psoriasis treatment after 1–2 weeks of irradiation.

2. The effects of NB-UVB on dendritic cells

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) in the immune system, playing a critical role in the initiation and regulation of immune responses. Their hallmark feature is the ability to robustly stimulate the proliferation of naïve T cells and to establish primary immune responses. In the treatment of skin diseases mediated by narrow-band UVB (NB-UVB), NB-UVB significantly reduces the number of CD11c+ DCs, particularly the CD1c−CD11c+ “inflammatory” DC subset, thereby improving the clinical outcomes in psoriasis. Studies by Erkin et al. have also demonstrated that NB-UVB irradiation not only decreases DC numbers but also diminishes the populations of other inflammatory cell types.

3. The regulatory effects of NB-UVB on immune cytokines in peripheral blood

In the normal human body, Th1 and Th2 cells maintain a balanced relationship. Numerous studies have demonstrated that an imbalance in the reciprocal interactions between Th1 and Th2 cytokines can lead to immune dysregulation, impairing the organism’s ability to mount an effective cellular immune response and thereby contributing to the onset, progression, and clinical outcomes of various diseases.

Wang Zhongyong and colleagues found that in patients with atopic dermatitis (AD), the levels of Th2‑type cytokines IL‑4 and IL‑13 in peripheral blood serum were significantly higher than those in healthy individuals. Following NB‑UVB phototherapy, the expression of IL‑4 and IL‑13 in peripheral blood serum decreased markedly, and after treatment, the differences in their levels compared with those in healthy controls were no longer statistically significant. These findings suggest that NB‑UVB corrects Th1/Th2 imbalance by suppressing the expression of IL‑4 and IL‑13. Metwally et al. also demonstrated that peripheral blood IL‑13 levels in AD patients were substantially elevated relative to healthy controls, and that these levels were positively correlated with disease severity and IgE concentrations. Walters et al. reported that NB‑UVB irradiation led to a marked reduction in circulating IL‑12 and IFN‑γ, indicating that NB‑UVB can attenuate IL‑12‑ and IFN‑γ‑mediated inflammatory responses and selectively decrease the release of proinflammatory cytokines by T cells in lesional skin.

In patients with vitiligo, IL‑10 secretion in peripheral blood is increased, with a statistically significant difference compared to the healthy control group, indicating a Th2‑dominant shift and suggesting an imbalance in the Th1/Th2 axis. Following NB‑UVB irradiation, IL‑10 levels decrease significantly, suggesting that NB‑UVB restores Th1/Th2 homeostasis by modulating IL‑10 secretion, thereby achieving a therapeutic effect.

In patients with hand eczema, the peripheral blood serum exhibits elevated levels of the Th1 cytokine interferon‑γ (IFN‑γ) and reduced levels of the Th2 cytokine interleukin‑4 (IL‑4). Following NB‑UVB phototherapy, IFN‑γ expression decreases while IL‑4 levels increase, suggesting that the dysregulated Th1/Th2 balance gradually returns to normal.

In patients with plaque psoriasis, the serum levels of TNF-α and IL‑8 were significantly higher than those in the healthy control group. Following NB‑UVB irradiation, the expression of both TNF‑α and IL‑8 decreased markedly, indicating that NB‑UVB can suppress the production of these cytokines in the serum of patients with plaque psoriasis. Furthermore, serum IFN‑γ levels were also elevated in psoriasis patients compared with healthy individuals; after NB‑UVB treatment, as clinical symptoms improved, the serum concentration of this cytokine declined. These findings suggest that NB‑UVB can reduce the levels of Th1‑type cytokines and help restore the Th1/Th2 balance.

In recent years, research has identified two additional CD4+ T-cell subsets: Th17 cells and Th22 cells. In inflammatory and autoimmune diseases, these cells play indispensable roles. Th17 cells primarily secrete IL‑17, IL‑22, IL‑17F, and IL‑6; by releasing these effector molecules, they generate a variety of pro‑inflammatory cytokines and chemokines, thereby contributing to immune and inflammatory responses. Th22 cells predominantly produce IL‑22 and are involved in maintaining skin homeostasis.

The proportion of Th17 cells in peripheral blood mononuclear cells is significantly elevated in patients with atopic dermatitis (AD). IL‑23 is a key cytokine in the differentiation and expansion of Th17 cells, and following NB‑UVB phototherapy, both Th17 cell numbers and IL‑23 expression are reduced. These findings suggest that downregulation of Th17 cells and their associated cytokines may represent one of the multiple immunological mechanisms underlying the therapeutic effects of NB‑UVB in AD.

In patients with plaque psoriasis, the proportions of Th17 and Th22 cells in peripheral blood mononuclear cells were significantly higher than in the healthy control group, and the serum levels of IL‑17A and IL‑22 were also markedly elevated. Following combined treatment with NB‑UVB irradiation and total glucosides of paeony, both the proportions of Th17 and Th22 cells in peripheral blood and the serum levels of IL‑17A and IL‑22 decreased significantly. These findings suggest that one mechanism of the combined therapy is the suppression of Th17 and Th22 cells in peripheral blood, which in turn attenuates the serum levels of IL‑17A and IL‑22, thereby controlling Th17- and Th22‑mediated inflammatory responses and effectively treating plaque psoriasis.

4. The regulatory effects of NB-UVB on peripheral blood chemokines and their receptors

Monocyte chemoattractant protein (MCP) is the earliest-discovered CC chemokine; its family comprises four major members: MCP‑1, MCP‑2, MCP‑3, and MCP‑4.

The expression levels of MCP‑1 in peripheral blood serum were higher in psoriasis patients than in the healthy control group, and the expression of CCR2 on peripheral blood mononuclear cells was also elevated. These findings suggest that the MCP‑1/CCR2 pathway contributes to the pathogenesis of psoriasis. Following NB‑UVB phototherapy, the expression levels of both MCP‑1 and CCR2 were significantly reduced; blocking the MCP‑1/CCR2 pathway inhibits the migration of inflammatory cells to other tissues, suppresses the release of pro‑inflammatory cytokines, and ultimately exerts a therapeutic effect in psoriasis. MCP‑4, upon binding to its specific receptor CCR2, becomes activated, thereby driving the recruitment and activation of monocytes and T cells, which play key roles in the inflammatory response of psoriasis. After NB‑UVB treatment, the expression levels of MCP‑4 are markedly decreased, which may help slow the progression of psoriasis.

CCR1 is a high‑affinity receptor for RANTES and MIP‑1α. In patients with psoriasis, CCR1 expression is elevated in peripheral blood neutrophils and is significantly downregulated following NB‑UVB phototherapy, concomitantly with a marked reduction in psoriatic skin lesions. These findings suggest that CCR1 contributes to neutrophil activation, chemotaxis, and the inflammatory response at sites of skin injury in psoriasis, and that the therapeutic efficacy of NB‑UVB is mediated by downregulation of this receptor. CCR2, upon binding its specific ligand MCP, can activate and recruit monocytes, T lymphocytes, and other cell types, thereby playing a role in inflammatory diseases. In patients with psoriasis, CCR2 is highly expressed in peripheral blood lymphocytes, and its expression is markedly reduced after NB‑UVB treatment, indicating that CCR2 may be involved in the activation and chemotaxis of psoriatic lymphocytes, driving the inflammatory response at lesion sites. NB‑UVB exerts its therapeutic effect by inhibiting this receptor.

Interferon‑induced T‑cell α‑chemokine (I‑TAC) belongs to the CXC chemokine family and exerts potent chemotactic activity toward T lymphocytes, particularly Th1 cells. In patients with plaque psoriasis, peripheral blood levels of I‑TAC are markedly elevated; following NB‑UVB phototherapy, clinical improvement is observed, accompanied by a significant reduction in I‑TAC expression in peripheral blood. These findings suggest that I‑TAC may be involved in the pathogenesis of psoriasis, and that both I‑TAC and its receptor CXCR3 play critical roles in the recruitment, infiltration, and maintenance of T lymphocytes.

Yu Juan and colleagues conducted an in-depth study of RANTES levels in the peripheral blood of patients with psoriasis. The results showed that RANTES expression was higher in the peripheral blood of these patients compared to the healthy control group, and that NB‑UVB irradiation significantly reduced RANTES levels after treatment. These findings suggest that RANTES may play a critical role in the pathogenesis of psoriasis. As one of the most important chemokines for T lymphocytes, the downregulation of RANTES induced by NB‑UVB likely decreases the number of T lymphocytes recruited to sites of skin injury, thereby attenuating the inflammatory response at the lesional skin.

5. Conclusion

The range of skin diseases treated with NB‑UVB is steadily expanding, yet it remains most commonly employed in the clinical management of psoriasis, atopic dermatitis, and vitiligo. Compared with conventional ultraviolet therapies, NB‑UVB demonstrates superior efficacy; however, its underlying mechanisms remain incompletely understood. Many studies have focused on cellular and molecular changes in lesional skin and peripheral blood, revealing that NB‑UVB exerts not only local effects at the site of skin lesions but also modulates systemic processes throughout the body. As basic research advances, it holds promise that the mechanisms by which NB‑UVB treats cutaneous disorders will be elucidated, enabling more effective clinical application.

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