Effective Treatment of Psoriasis with Narrow-Band UVB Phototherapy Is Linked to Suppression of the IFN and Th17 Pathways

Abstract

Narrow-band ultraviolet-B (NB-UVB) phototherapy is an effective treatment for psoriasis. The molecular mechanisms underlying its efficacy are incompletely understood. To identify NB-UVB-induced molecular pathways that may account for its anti-inflammatory efficacy, gene expression profiling was performed using epidermal RNA from lesional and nonlesional skin from patients with psoriasis undergoing NB-UVB therapy. Downregulation of Th17 signaling pathway was observed during NB-UVB therapy in psoriatic epidermis. Strong inhibition of the Th17 pathway by UVB was confirmed in an ex vivo organ culture system by demonstrating reduced signal transducer and activator of transcription 3 (STAT3) phosphorylation and β-defensin-2 production. These results were further substantiated by demonstrating that NB-UVB inhibited the Th17-dependent psoriasis-like dermatitis in mice. Other pathways affected by NB-UVB therapy include the IFN signaling pathway, epidermal differentiation, and other well-known therapeutic targets in psoriasis, such as the glucocorticoid, vitamin D, peroxisome proliferator-activated receptor, and IL-4 signaling pathways. In conclusion, clinical improvement of psoriasis by NB-UVB is linked to suppression of Th17 and type I and type II IFN signaling pathways, which are critical in the pathogenesis of the disease. Our results show that clinically effective NB-UVB therapy is based on suppression of a broad range of important molecular pathways in psoriatic skin.

Epidermal Th22 and Tc17 Cells Form a Localized Disease Memory in Clinically Healed Psoriasis

“…Taken the available data on circulating T cells during biologics (39,40) and nb-UVB treatment (41,42) it is not possible to predict whether replenishment of skin T cells occur in the different treatments. The inflammatory profiles in epidermal T cells may seem contradictory to previous publications where expression analysis of full skin biopsies 6 wk after nb-UVB treatment suggested normalization of IL17A and IL22 gene expression (43,44) and highlights the importance of dissecting different T cell populations present within the different anatomical compartments of the skin.…”

Systemic treatment and narrowband ultraviolet B differentially affect cardiovascular risk markers in psoriasis

“…However, the literature is controversial and both we and others have shown a lack of effect by UV therapy on the studied cytokines. 35,44,45 It should be remembered that the relationship between local inflammation and systemic inflammation is complex, and that an influence from the skin inflammation may affect the systemic cardiovascular risk. This is demonstrated by hs-CRP, which is a systemic marker of cardiovascular risk but which strongly correlates to disease severity measured by PASI and is reduced along with skin symptoms, for example upon UVB treatment.…”

“…NB-UVB suppresses the interferon and Th17-signaling pathways in the skin. 35 Moreover, keratinocyte apoptosis is a mechanism of action of NB-UVB in psoriatic epidermis. 36 We demonstrate that, in spite of clinical improvements in psoriasis skin symptoms, patients receiving NB-UVB treatment display continuously high levels of circulating cardiovascular risk markers, supporting the hypothesis that the effect of the treatment is localized to the skin.…”

The efficacy of microphototherapy with a MedLight CupCUBEGrimed device in psoriatic patients with localized lesions

“…Decreased IFN-γ expression and increased in IL-4 production after UVB irradiation lead to decreased local immunoreactivity, which forms the therapeutic effects of UVB on psoriasis. Moreover, UVB irradiation has inhibitory effects on the IL-23/IL-17 axis, which exhibits an important pathway in psoriasis pathogenesis (12). In conclusion, UVB therapy is associated with downregulation of type 1 and type 2 IFN signaling pathways (IL-12, IFN-γ, IL-8) and suppression of the IL-23/IL-17 axis while immunosuppressive cytokines as IL-4, IL-6, IL-10 increase.…”