کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5649377 1407123 2017 31 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Immunostimulatory Endogenous Nucleic Acids Drive the Lesional Inflammation in Cutaneous Lupus Erythematosus
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Immunostimulatory Endogenous Nucleic Acids Drive the Lesional Inflammation in Cutaneous Lupus Erythematosus
چکیده انگلیسی
Cutaneous lupus erythematosus (CLE) is a photosensitive autoimmune disease characterized by a strong type I IFN-associated inflammation. Keratinocytes are known to determine the interface dermatitis pattern in CLE by production of proinflammatory cytokines in the lower epidermis. These cytokines drive a cytotoxic anti-epithelial immune response resulting in keratinocytic cell death and release of endogenous nucleic acids. We hypothesized that these endogenous nucleic acids (RNA and DNA motifs) have the capacity to activate innate immune pathways in keratinocytes via pathogen recognition receptors. Gene expression analyses showed an excessive activation of innate immune response pathways with strong expression of IFN-regulated cytokines in CLE skin lesions. Cultured keratinocytes produce large amounts of these cytokines in response to stimulation of PRR with endogenous nucleic acids. UV stimulation enhances the immunogenicity of endogenous nucleic acids and induces CLE-like skin lesions in knockout mice lacking the cytosolic DNase TREX1. Our results provide evidence for a pathogenetic role of endogenous nucleic acids in CLE. They are released within the cytotoxic inflammation along the dermo-epidermal junction and have the capacity to drive the CLE-typical inflammation. UV irradiation supports this inflammation by generation of highly immunostimulatory DNA motifs (8-hydroxyguanosine). These findings explain the photosensitivity of patients with lupus and identify pathways of the innate immune system as targets for future therapies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 137, Issue 7, July 2017, Pages 1484-1492
نویسندگان
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