Whole-Genome Expression Profiling in Skin Reveals SYK As a Key Regulator of Inflammation in Experimental Epidermolysis Bullosa Acquisita

Frontiers in Immunology
Unni SamavedamRalf Ludwig

Abstract

Because of the morbidity and limited therapeutic options of autoimmune diseases, there is a high, and thus far, unmet medical need for development of novel treatments. Pemphigoid diseases, such as epidermolysis bullosa acquisita (EBA), are prototypical autoimmune diseases that are caused by autoantibodies targeting structural proteins of the skin, leading to inflammation, mediated by myeloid cells. To identify novel treatment targets, we performed cutaneous genome-wide mRNA expression profiling in 190 outbred mice after EBA induction. Comparison of genome-wide mRNA expression profiles in diseased and healthy mice, and construction of a co-expression network identified Sykb (spleen tyrosine kinase, SYK) as a major hub gene. Aligned, pharmacological SYK inhibition protected mice from experimental EBA. Using lineage-specific SYK-deficient mice, we identified SYK expression on myeloid cells to be required to induce EBA. Within the predicted co-expression network, interactions of Sykb with several partners (e.g., Tlr13, Jdp2, and Nfkbid) were validated by curated databases. Additionally, novel gene interaction partners of SYK were experimentally validated. Collectively, our results identify SYK expression in myeloid cells as a requi...Continue Reading

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Citations

Jul 18, 2019·Journal of the European Academy of Dermatology and Venereology : JEADV·K KridinK T Amber
Apr 21, 2020·Immunotherapy·Alvise SernicolaMauro Alaibac
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May 28, 2019·Frontiers in Immunology·Kentaro IzumiRalf J Ludwig
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Jan 29, 2019·Frontiers in Medicine·Hiroshi KogaKatja Bieber
Jan 29, 2021·Frontiers in Immunology·Katja BieberRalf J Ludwig
May 26, 2020·The Journal of Investigative Dermatology·Pia StüsselKatja Bieber
Apr 8, 2021·Deutsches Ärzteblatt International·Nina van BeekEnno Schmidt
Jul 11, 2021·Indian Journal of Dermatology, Venereology and Leprology·Anuradha BishnoiRahul Mahajan
Aug 10, 2021·Deutsches Ärzteblatt International·Nina van BeekEnno Schmidt
Nov 7, 2021·Experimental Dermatology·Stefan TukajMichael Kasperkiewicz

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Methods Mentioned

BETA
biopsies
ELISA
flow cytometry
light microscopy
FCS
FACS
protein assay

Software Mentioned

R
[UNK]
R DCGL package
DAVID
SigmaPlot
limma R
ImageJ

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