Photohardening of polymorphic light eruption patients decreases baseline epidermalLangerhans cell density while increasing mast cell numbers in the papillary dermis

Abstract

The pathogenesis of polymorphic light eruption (PLE) has been linked to a lack of UV-induced immune suppression. To determine the role of Langerhans cells (LC), mast cells and regulatory T cells, biopsies from PLE patients were taken from exposed sites in spring before and after photohardening with 311 nm or PUVA as well as again in summer. Skin sections were assessed for the presence of Langerin/CD1a+ LC and CD3+, CD4+, CD25+ or FoxP3+ T cells and mast cells. Photohardening transiently decreased the density of epidermal LC and significantly increased a low baseline mast cell density in the papillary dermis of PLE patients. Baseline T cell numbers in the skin were low, and there was no difference in PLE patients among any time point. This suggests that LC suppression together with recruitment of mast cells into photohardened skin may be a key cellular event underlying the mechanism by which phototherapy protects from PLE.

Serotonin signalling is crucial in the induction of PUVA‐induced systemic suppression of delayed‐type hypersensitivity but not local apoptosis or inflammation of the skin

“…Biocare Mach 2 Double stain 2, developed with Biocare Vulcan Fast red, or DAB from Dako (K5001) was performed according to the manufacturer's instructions. Giemsa staining was performed according to the standard protocol . Sections from a carcinoid tumor and normal intestinal mucosa (with enterochromaffin cells) served as positive controls for 5‐HT staining.…”

Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference?

“…Moreover, impaired Langerhans cell migration in psoriasis was normalized after effective treatment (with TNF inhibitors, ustekinumab or fumaric acid), irrespective of the agent administered . The resetting of the capacity of Langerhans cells to emigrate from the skin to lymph nodes may be a particular component of the therapeutic effect of UV in psoriasis, similar to the result of photohardening in patients with PLE, in whom the migratory capacity of Langerhans cells normalizes after repetitive treatment with suberythemal UVB . Photohardening may affect the complex cytokine milieu in the skin and thereby normalizing cellular migration processes after subsequent UV exposure (Table ).…”

“…Systemic alterations induced by phototherapy may help to prime the microenvironment in the skin but they are insufficient to produce clearance of psoriatic lesions. In this context, UV phototherapy diminishes the number of Langerhans cells in the skin that may significantly contribute to its antipsoriatic properties by taking away stimuli such as the production and release of nitric oxide and epidermal growth factor which regulate keratinocyte proliferation . Moreover, impaired Langerhans cell migration in psoriasis was normalized after effective treatment (with TNF inhibitors, ustekinumab or fumaric acid), irrespective of the agent administered .…”

The alternative complement component factor B regulates UV-induced oedema, systemic suppression of contact and delayed hypersensitivity, and mast cell infiltration into the skin

“…18 This alteration to mast cell traffic is important not only for photocarcinogenesis 29 but is also associated with successful phototherapy in polymorphic light eruption patients. 30 Our results suggest that activation of the alternative complement pathway is another potential mechanism by which mast cell movements are regulated by UV. While exposure to ssUV caused a significant increase in dermal mast cells 6 h later in wild type mice as expected, this failed to occur in fB−/− mice.…”