Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of target genes involved in many cellular functions including cell proliferation, differentiation and immune/inflammation response. The PPAR subfamily consists of three isotypes: PPAR alpha, PPAR beta/delta and PPAR gamma, which have all been identified in keratinocytes. PPAR beta/delta is the predominant subtype in human keratinocytes, whereas PPAR alpha and PPAR gamma are expressed at much lower levels and increase significantly upon keratinocyte differentiation. PPAR beta/delta is not linked to differentiation, but is significantly upregulated upon various conditions that result in keratinocyte proliferation, and during skin wound healing. In vitro and in vivo evidence suggests that PPARs appear to play an important role in skin barrier permeability, inhibiting epidermal cell growth, promoting epidermal terminal differentiation and regulating skin inflammatory response by diverse mechanisms. These proprieties are pointing in the direction of PPARs being key regulators of skin conditions characterized by hyperproliferation, inflammatory infiltrates and aberrant differentiation such as psoriasis, but may also have clinical implications in inflammatory skin disease (e.g. atopic dermatitis), proliferative skin disease, wound healing, acne and protease inhibitor associated lipodystrophia.

Dendritic cells (DC) are potent antigen-presenting cells (APC). Ongoing preclinical and clinical studies exploit this capacity for the immunotherapy of tumors. We tested vaccinia virus (VV) as a vector to transduce human DC. Immature and mature DC were prepared from blood monocytes and infected with (1)

ADA + C/B resulted in more rapid and higher efficacy within the first 4 weeks; thereafter, the trend was towards a higher response with ADA monotherapy. There was no statistical difference in the PASI 75 response at week 16. Both treatment regimens were well tolerated.

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Consistent with prior evidence indicating that subepidermal blister formation in BP is dependent upon complement activation, the frequent finding of complement-fixing IgG1 autoantibodies to both the ECD and ICD of BP180 might have pathogenic relevance in BP. These findings provide new insights relevant for our understanding of the immune response to BP180, the putative key autoantigen in BP.