Journal article
Langerhans cells are an essential cellular intermediary in chronic dermatitis
H Anderton, M Chopin, CA Dawson, SL Nutt, L Whitehead, N Silke, N Lalaloui, J Silke
Cell Reports | Published : 2022
Open access
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 ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank the staff of the WEHI Bioservices and histology facilities for practical assistance. This work was funded by NHMRC grants 1046984 (J.S., 2013-2016), 1105023 (J.S. 2016-2018), and 1155342 (S.L.N.), fellowships 1058190 (J.S., 2014-2018), 1107149 (J.S., 2016-2020), and 1194144 (H.A., 2020-2022), and scholarship 1093637 (H.A., 2015-2018); Australian Government Research Training Program Scholarships (H.A. and C.A.D.); the Jenny Thatchell/Pauline Speedy and the Barbara McDonald Innovation grants (M.C.); and donations from George Janko & Karen Inge Foundation and Thomas William Francis and Violet Coles Trust and was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (GNT9000719).