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Effects of narrow-spectrum uvb treatment on skin immune cells and cytokines

01/17/2019

Narrow-spectrum UVB (NB-UVB) is effective in the treatment of some skin diseases, but the mechanism of treatment is still unclear.Studies have shown that nb-uvb can effectively reduce the number of immune cells, inhibit the production of cytokines, and achieve the effect of treating some skin diseases.This article reviews the effects of NB-UVB on the expression of immune cells and cytokines in common skin diseases.

Ultraviolet radiation therapy is widely used in dermatology clinic, and the biological effects of different wavelengths of ultraviolet radiation are also different.In a narrow spectrum of the 311 ~ 313 nm wavelength UVB rays (narrow – bandultraviolet – B, NB – UVB) strong penetrability, skin erythema effect is small, not easy to burn the skin, and not easy to induce DNA mutations, is widely used for psoriasis, vitiligo, atopic dermatitis, skin T cell lymphoma, itching, compressed moss, seborrheic dermatitis and other difficult clinical healing skin diseases.So far, it is still unclear whether nb-uvb exerts local effect or overall systemic effect. Existing studies have shown that nb-uvb can effectively reduce the number of immune cells such as T cells and dendritic cells, inhibit the production of cytokines, and thus play a therapeutic role in skin diseases.In this article, NB-UVB mediated the expression of skin immune cells and cytokines, and promoted the treatment of skin diseases.

  1. Effects of NB-UVBon skin T lymphocytes

The etiology of some skin diseases such as vitiligo and psoriasis is unknown, but they are closely related to immunity. In the development process of these diseases, T lymphocytes are involved in the pathological process.Animal experiments and clinical treatments have found that activation of CD4+ and CD8+ cells is necessary for the occurrence and development of immune skin diseases, and both of them require interaction with dendritic cells.Most of the therapeutic effects of NB-UVB on skin diseases may be related to its immunosuppressive function.The experiment showed that the radiation intensity of 0.28 ~ 2J/cm2 nb-uvb, three times a week systemic treatment, can effectively inhibit the activation of CD4+ helper T cells in patients with vitiligo, but also promote the regulation of T cell activity, is conducive to the recovery of patients;NB-UVB irradiation twice a week combined with 0.1% tacrolimus for topical use is more effective in the treatment of segmental vitiligo.Comparative studies have shown that UVB with a wavelength of 312nm of 50-100mj /cm2 can better induce the apoptosis of T cells in psoriasis plaque than UVB with a wavelength of 290-320nm. After 1-2 weeks of irradiation, the therapeutic effect of psoriasis can be effectively improved.

  1. The effects of NB-UVBon dendritic cells

Dendriticcell (DC), a most powerful professional antigen presenting cell (APC) in the immune system of the body, plays an important role in initiating and regulating the immune response.The greatest characteristic of DC is that it can significantly stimulate the proliferation of primary T cells and establish a primary immune response.In the treatment of skin diseases mediated by nb-uvb, nb-uvb significantly reduces the number of CD11c+DCs, especially cd1c-cd11c + “inflammatory” DCs, so as to improve the clinical effect of psoriasis.Erkin et al. also found that in addition to reducing the number of DCs, nb-uvb irradiation also reduced the number of other inflammatory cells.

  1. Regulation of immune cytokines in peripheral blood by NB-UVB

In normal human body, Th1 and Th2 balance each other.Many studies have shown that the imbalance of Th1/Th2 cytokine interaction will lead to immune disorders, which will result in the body’s inability to carry out effective cellular immune response, thus leading to or affecting the occurrence, development and outcome of a variety of diseases.

Wang zhongyong et al. found that the expression levels of Th2 cytokines il-4 and il-13 in peripheral blood serum of patients with atopic dermatitis (AD) were significantly higher than that of normal people. After nb-uvb radiation treatment, the expression levels of il-4 and il-13 in peripheral blood serum were significantly reduced, while the expression levels of il-4 and il-13 in serum of patients with AD were not statistically significant.The above results show that nb-uvb can correct the imbalance of Th1/Th2 by inhibiting the expression of il-4 and il-13.Metwally et al. also showed that the level of il-13 in peripheral blood of AD patients was significantly higher than that of the normal control group, and its expression level was positively correlated with the severity of the disease and IgE level.

Walters et al. found that the number of il-12 and ifn-gamma in the blood was significantly reduced after nb-uvb irradiation, indicating that nb-uvb can inhibit the inflammatory response mediated by il-12 and ifn-gamma, and selectively reduce the release of pro-inflammatory cytokines by T cells in the skin injury area. The increase of il-10 secretion in the peripheral blood of patients with vitiligo was statistically significant compared with that of the normal control group. The presence of Th2 deviation indicated the imbalance of Th1/Th2.After nb-uvb irradiation, the level of il-10 was significantly reduced, suggesting that nb-uvb restored Th1/Th2 balance by affecting the secretion of il-10, achieving therapeutic effect.

In patients with hand eczema, the expression level of Th1 cytokines in peripheral blood serum was increased, while the expression level of Th2 cytokines was decreased. After nb-uvb radiation treatment, the expression level of inf-gamma was decreased and the level of il-4 was increased, suggesting that the imbalance of Th1/Th2 gradually tended to be normal.

The expression levels of TNF- and il-8 in serum of patients with psoriasis vulgare were significantly higher than those in the normal control group. The expression levels of TNF- and il-8 in serum of patients with psoriasis vulgare were significantly decreased after nb-uvb irradiation treatment, indicating that nb-uvb can inhibit the expression of TNF- and il-8 in serum of patients with psoriasis vulgare.The expression of IFN- in serum of patients with psoriasis was also found to be higher than that of normal people.These results suggest that nb-uvb can reduce the amount of Th1 cytokines and correct the imbalance effect of Th1/Th2.

Two other CD4+T cell subsets have been identified in recent years :Th17 cells and Th22 cells.Th17 cells and Th22 cells play irreplaceable roles in inflammatory diseases and autoimmune diseases.Th17 cells mainly secrete il-17, il-22, il-17f, il-6, and Th17 cells produce a variety of pro-inflammatory cytokines and chemokines by secreting these effector molecules, which are involved in the immune response and inflammatory response of the body.Th22 cells mainly secrete il-22, which is involved in skin self-regulation.

The proportion of Th17 in peripheral blood monocytes of AD patients was significantly increased, and il-23 was the key cytokine in the production process of Th17 cells. After nb-uvb radiation treatment, the expression levels of Th17 and il-23 in patients were decreased.The results suggest that reducing the expression of Th17 cells and related cytokines may be one of the many immune mechanisms of nb-uvb irradiation in the treatment of AD.

  1. The regulatory effect of NB-UVBon peripheral blood chemokines and their receptors

Monocyte chemotactic protein (MCP) is the earliest cc-type chemotactic factor, and its family members are mainly 4, namely McP-1, McP-2, McP-3 and McP-4.

The expression level of McP-1 in peripheral blood serum of patients with psoriasis was higher than that of the healthy group, and the expression level of CCR2 in peripheral blood mononuclear cells was also higher than that of the healthy group, suggesting that the McP-1 /CCR2 pathway is involved in the pathogenesis of psoriasis.After nb-uvb radiation treatment, the expression levels of McP-1 and CCR2 were significantly reduced, blocking the McP-1 /CCR2 pathway, thereby inhibiting the infiltration of inflammatory cells to other places, preventing the release of inflammatory factors, and finally playing a role in the treatment of psoriasis.McP-4 is activated by binding to the specific receptor CCR2, thereby driving monocytes and T cells to play a role in the inflammatory response of psoriasis.After NB-UVB irradiation treatment, its expression level decreased significantly, which can delay the pathogenesis of psoriasis.

CCR1 is a high affinity receptor of RANTES and mip-1. The expression of CCR1 in peripheral blood neutrophils of patients with psoriasis is increased, and the expression is significantly down-regulated after nb-uvb radiation treatment, and the psoriasis lesions are also significantly reduced.These results suggest that CCR1 is involved in the activation and chemotaxis of neutrophils in psoriasis, as well as the inflammatory reaction at the site of skin injury. The effective treatment of nb-uvb is achieved by reducing the expression of this receptor.CCR2, when combined with specific ligand MCP, can activate and chemotactic monocytes, T lymphocytes, etc. and play a role in inflammatory diseases.CCR2 is highly expressed in peripheral blood lymphocytes of patients with psoriasis, and the expression of this receptor is significantly decreased after nb-uvb irradiation treatment, suggesting that CCR2 may be involved in the activation and chemotaxis of lymphocytes in psoriasis, leading to inflammatory reactions in the skin lesions of patients.NB-UVB plays a therapeutic role by inhibiting this receptor.

Interferon-induced T cell chemotactic factor (i-tac) belongs to CXC chemotactic factor and has strong chemotactic effect on T lymphocytes, especially Th1 cells.In patients with psoriasis vulgis, the level of i-tac in peripheral blood was significantly increased. After nb-uvb radiation treatment, the condition of patients was significantly improved, and the expression of i-tac in peripheral blood was also significantly decreased.This conclusion suggests that i-tac may be involved in the pathogenesis of psoriasis, and that i-tac and its receptor CXCR3 play an important role in the aggregation, infiltration and maintenance of T lymphocytes.

Yu Juan et al. conducted an in-depth study on RANTES in peripheral blood of patients with psoriasis.The results showed that the expression of RANTES in patients’ peripheral blood was higher than that in the normal group, and the expression of RANTES in patients’ peripheral blood was significantly reduced after nb-uvb radiation treatment, suggesting that RANTES may play a key role in the pathogenesis of psoriasis.As one of the most important chemotactic factors of T lymphocytes, RANTES is down-regulated by nb-uvb, which is likely to reduce the number of T lymphocytes chemotactic to the site of skin injury and reduce the inflammatory response in the site of skin injury.

  1. Conclusion

There are more and more types of nb-uvb in the treatment of skin diseases, but it is relatively common in the clinical treatment of psoriasis, atopic dermatitis and vitiligo.Compared with traditional ultraviolet therapy, nb-uvb is more effective, but its therapeutic mechanism is still unclear. Many studies focus on the study of cells and related factors in skin lesions and peripheral blood. These studies show that nb-uvb not only plays a local effect on the skin lesions, but also can affect the overall system of the body.With the deepening of basic research, it is expected to reveal the mechanism of nb-uvb in the treatment of skin diseases and better apply it in clinical practice.

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