University of Oulu

Outi Lindgren, Gwenaëlle Le Menn, Jussi Tuusa, Zhi Jane Chen, Kaisa Tasanen, Nina Kokkonen, Absence of NC14A Domain of COLXVII/BP180 in Mice Results in IL-17‒Associated Skin Inflammation, Journal of Investigative Dermatology, Volume 143, Issue 1, 2023, Pages 48-56.e7, ISSN 0022-202X,

Absence of NC14A domain of COLXVII/BP180 in mice results in IL-17‒associated skin inflammation

Saved in:
Author: Lindgren, Outi1,2,3; Le Menn, Gwenaëlle4; Tuusa, Jussi1,3;
Organizations: 1Department of Dermatology, PEDEGO Research Unit, University of Oulu, Oulu, Finland
2Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
4Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.7 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2023-08-09


The deletion of exon 18 from Col17a1 in transgenic ΔNC14A 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 ΔNC14A 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 dermo‒epidermal junction of symptomatic ΔNC14A mice. Elevated gene expression of IL-17‒associated 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 ΔNC14A mice. The proportions of B cells and regulatory T cells were increased in lymph nodes. An 8-week treatment with an anti‒IL-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-17‒associated inflammation in the skin.

see all

Series: Journal of investigative dermatology
ISSN: 0022-202X
ISSN-E: 1523-1747
ISSN-L: 0022-202X
Volume: 143
Issue: 1
Pages: 48 - 56.e7
DOI: 10.1016/j.jid.2022.07.019
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This study was financially supported by grants from the Academy of Finland (grant numbers 294738 and 330822 to KT and 325965 to ZJC); the Sigrid Juselius Foundation; the University of Oulu Graduate School; and the Medical Research Center, Oulu University Hospital (Oulu, Finland).
Academy of Finland Grant Number: 294738
Detailed Information: 294738 (Academy of Finland Funding decision)
330822 (Academy of Finland Funding decision)
325965 (Academy of Finland Funding decision)
Copyright information: © 2022 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an open access article under the CC BY license (