| First Author | Lindgren O | Year | 2023 |
| Journal | J Invest Dermatol | Volume | 143 |
| Issue | 1 | Pages | 48-56.e7 |
| PubMed ID | 35985497 | Mgi Jnum | J:358957 |
| Mgi Id | MGI:7345331 | Doi | 10.1016/j.jid.2022.07.019 |
| Citation | Lindgren O, et al. (2022) Absence of NC14A Domain of COLXVII/BP180 in Mice Results in IL-17Associated Skin Inflammation. J Invest Dermatol |
| abstractText | The deletion of exon 18 from Col17a1 in transgenic DeltaNC14A mice results in the absence of the NC14A domain. NC14A corresponds to the human NC16A domain, the immunodominant epitope in bullous pemphigoid. Before the age of 1 year, 84% of DeltaNC14A mice have developed severe itch and skin erosion. Further characterization of mice with mutated CoLXVII (Bp180) revealed acanthosis; subepidermal blistering; and inflammatory cell infiltrates, especially neutrophils, eosinophils, and mast cells in the lesional skin. Direct immunofluorescence analysis detected linear complement C3, IgG, and/or IgA deposition in the dermoepidermal junction of symptomatic DeltaNC14A mice. Elevated gene expression of IL-17associated cytokines was detected in the lesional skin. An increased proportion of dendritic cells, myeloid-derived suppressor cells, and NK cells and a decrease of T cells were found in both the spleen and lymph nodes of symptomatic DeltaNC14A mice. The proportions of B cells and regulatory T cells were increased in lymph nodes. An 8-week treatment with an antiIL-17A decreased the expression of Il6, Il23a, and Cxcl1 in the nonlesional skin. Our results suggest that the absence of the NC14A domain of CoLXVII in mice causes an autoimmune response against the cutaneous basement membrane and manifests as an IL-17associated inflammation in the skin. |
