Bullous pemphigoid (BP) is an autoimmune subepidermal blistering skin disease where autoantibodies are developed against BP180 (also known as collagen XVII, colXVII). Our group has previously developed a transgenic mouse line, ΔNC14A mice, in which deletion of exon 18 in Col17a1 results in the absence of NC14A domain, corresponding to human NC16A domain, the main autoantigen in BP. ColXVII levels in skin are decreased and during aging ΔNC14A mice develop severe itch, blisters, and skin erosion similarly to BP patients. Our aim was to further characterize the inflammation and autoimmunization in ΔNC14A mice. In histological analysis of the lesional skin we detected acanthosis, subepidermal blistering and mixed inflammatory cell infiltrate, especially neutrophils and mast cells. In direct immunofluorescence symptomatic ΔNC14A mice showed linear deposition of complement C3, IgG (IgG1, IgG2b and IgG3) and/or IgA in the dermo-epidermal junction. Quantitative real-time PCR studies revealed increased expression of Il1b, Il6, Il17a, Il23a, Il36a, and Il36g in the lesional skin and increased IL-17A levels in serum were detected by ELISA. Inflammatory cell populations in spleen and draining lymph nodes were analysed by flow cytometry. Symptomatic ΔNC14A mice had increased proportion of effector T cells, myeloid derived suppressor cells and CD11b+ myeloid cells in both spleen and lymph nodes. In addition, proportion of B cells was increased in lymph nodes. Because anti-IL-17A-therapy has a potential as BP treatment we treated six symptomatic ΔNC14A mice with anti-IL-17A. The treatment restrained symptoms, but histologically inflammation was similar to untreated lesional skin. Our results suggest that structural modifications of colXVII reflect the state in BP skin where autoimmune reaction results in the decrease of colXVII and blister formation. Thus, ΔNC14A mouse line could be further utilized as a potential BP-model.

ESDR034 - Dysfunctional Collagen XVII provokes skin inflammation

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING