PXD052619

PXD052619 is an original dataset announced via ProteomeXchange.

Title	The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients
Description	Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). Objective: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T-cell and humoral immune response against the extracellular serine protease (Esp). Methods: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T-cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T-cells reacting to Esp were detectable in both AD patients and healthy controls. The T-cell response in healthy adults was characterized by IL-17, IL-22, IFN-gamma, and IL-10, whereas the AD patients' T-cells lacked IL-17 production and released only low amounts of IL-22, IFN-gamma, and IL-10. In contrast, Th2 cytokine release was higher in T-cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusions: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T-cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.
HostingRepository	MassIVE
AnnounceDate	2024-05-28
AnnouncementXML	Submission_2024-05-28_04:37:33.913.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Leif Steil
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Staphylococcus epidermidis; NCBI TaxID: 1282;
ModificationList	Dimethyl; Dimethyl:2H(4)13C(2)
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-28 02:08:13	ID requested
⏵ 1	2024-05-28 04:37:34	announced

no publication

submitter keyword: Esp, Staphylococcus epidermidis, atopic dermatitis, allergy, IgE, Th2, protease

Dr. Leif Steil
contact affiliation	Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
contact email	steil@uni-greifswald.de
lab head
Leif Steil
contact affiliation	university medicine greifswald
contact email	steil@uni-greifswald.de
dataset submitter

MassIVE dataset URI

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