Langerhans cells are an essential cellular intermediary in chronic dermatitis
- Author(s)
- Anderton, H; Chopin, M; Dawson, CA; Nutt, SL; Whitehead, L; Silke, N; Lalaloui, N; Silke, J;
- Details
- Publication Year 2022-06-07,Volume 39,Issue #10,Page 110922
- Journal Title
- Cell Reports
- Abstract
- SHARPIN regulates signaling from the tumor necrosis factor (TNF) superfamily and pattern-recognition receptors. An inactivating Sharpin mutation in mice causes TNF-mediated dermatitis. Blocking cell death prevents the phenotype, implicating TNFR1-induced cell death in causing the skin disease. However, the source of TNF that drives dermatitis is unknown. Immune cells are a potent source of TNF in vivo and feature prominently in the skin pathology; however, T cells, B cells, and eosinophils are dispensable for the skin phenotype. We use targeted in vivo cell ablation, immune profiling, and extensive imaging to identify immune populations driving dermatitis. We find that systemic depletion of Langerin(+) cells significantly reduces disease severity. This is enhanced in mice that lack Langerhans cells (LCs) from soon after birth. Reconstitution of LC-depleted Sharpin mutant mice with TNF-deficient LCs prevents dermatitis, implicating LCs as a potential cellular source of pathogenic TNF and highlighting a T cell-independent role in driving skin inflammation.
- Publisher
- Cell Press
- Keywords
- Animals; *Dermatitis/pathology; Inflammation/pathology; *Langerhans Cells; Mice; Mice, Knockout; Skin/metabolism; Tumor Necrosis Factor-alpha/metabolism; CP: Immunology; Lubac; Langerhans cells; Sharpin; Tnf; apoptosis; cell death; dermatitis; inflammation; innate immunity; skin
- Research Division(s)
- Inflammation; Immunology; Advanced Technology And Biology
- PubMed ID
- 35675765
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2022.110922
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2022.110922- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-06-17 09:28:40
Last Modified: 2022-06-17 09:41:38