INTRODUCTION
Psoriasis, eczema and other immune-mediated skin diseases arise in the context of cutaneous inflammation.1 The majority of treatments for these conditions target the effector arm of the immune response, including pathogenic T cells, Antigen Presenting Cells (APC’s), and pro-inflammatory cytokines.2 Immunosuppressive and newer targeted immune-modulating therapies such as anti-TNFα and anti-IL-12/23 antibodies are widely used in dermatology. Since these medications only target the effector immune response, discontinuation of the medication often leads to reappearance of the skin lesions.3 In this article, we review the mechanisms through which phototherapy induces local cutaneous immune modulation and leads to therapeutic efficacy for many dermatologic diseases.
METHODS
A literature review using PubMed and the keywords: “Ultraviolet OR Phototherapy†AND “Immunosuppression OR Inflammation†was performed. Only articles relating to box phototherapy were used; studies with the Excimer Laser were not included. Articles with English language abstracts from 1997-2012, as well as references used by these articles, were included.
RESULTS
Mechanism 1: Phototherapy Directly Targets the Effector Immune System, Including Th22 Cells
Like many immunosuppressive therapies utilized for the treatment of cutaneous inflammatory diseases such as psoriasis and eczema, phototherapy targets the effector arm of the immune system (Figure 1).
Phototherapy directly targets the T cells, which drive skin inflammation in psoriasis and atopic dermatitis. Phototherapy effectively decreases T cell-mediated inflammation in both diseases by inhibiting T cell activation (Figure 1). Psoriasis is largely driven by Th17 and Th22 cells, both of which produce the cytokine IL-22.4 Interestingly, the IL-22 cytokine and Th22 cells appear to also be pathogenic in atopic dermatitis, along with the more well-described Th2 cells. IL-22 drives cutaneous disease by inhibiting terminal differentiation of keratinocytes and disrupting the epidermal barrier.5 Compared to healthy skin, psoriatic and atopic dermatitis skin lesions demonstrate greatly increased levels of IL-22.6 Levels of cutaneous IL-22 are decreased in the skin of atopic dermatitis patients following NB-UVB therapy,7 highlighting the inhibition of cutaneous effector T cell activation.
APC’s of the skin are important modulators of inflammatory skin disease. Phototherapy has a direct effect on APC’s by damaging their DNA.8,9,10 This DNA damage results in several significant changes. First, APC’s from UV-irradiated skin show diminished dendritic networks, which impairs their immune modulating capabilities.11 Second, these APC’s show decreased expression of both MHC molecules (signal one) and costimulatory molecules (signal two), rendering them unable to effectively interact with T cells.11 As a result, APC’s after UV treatment are functionally impaired and unable to help mount effective T cell responses, decreasing pathogenic T cells in the epidermis.9 Finally, UV treatment also appears to increase the migration of APC’s from the skin to the draining lymph node. This migration effectively
