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\begin{document}

\title{The extracellular serine protease from Staphylococcus epidermidis
elicits a type 2 immune response in atopic dermatitis patients}



\author[1]{Goran Abdurrahman}%
\author[2]{Rebecca Pospich}%
\author[1]{Leif Steil}%
\author[1]{Manuela Gesell Salazar}%
\author[1]{Juan Izquierdo González}%
\author[1]{Nicole Normann}%
\author[1]{Daniel Mrochen}%
\author[3]{Christian  Scharf}%
\author[1]{Uwe Völker}%
\author[4]{Thomas Werfel}%
\author[1]{Barbara Bröker}%
\author[2]{Lennart Roesner}%
\author[1]{Lidia Gomez Gascón}%
\affil[1]{University Medicine Greifswald}%
\affil[2]{Medical University of Hanover}%
\affil[3]{University medicine Greifswald}%
\affil[4]{Medical University Hanover}%


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  \date{May 20, 2024}


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\begin{abstract}
Background: Atopic dermatitis (AD) is a chronic inflammatory skin
disease caused by skin barrier defects and a misdirected type 2 immune
response against antigens. The skin microbiome in AD is characterised by
a reduction in microbial diversity with a dominance of staphylococci,
including Staphylococcus epidermidis (S. epidermidis). To assess whether
S. epidermidis antigens play a role in AD, we studied the immune
response against the extracellular serine protease (Esp). Methods: We
analyzed the binding of human IgG4 to S. epidermidis extracellular
proteins using immunoblotting and mass spectrometry. We then measured
serum antibodies specific for 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 IgG4-binding antigen of S. epidermidis. Esp-specific IgE
was present in human serum; AD patients had higher concentrations than
controls. The T cell response to Esp in healthy adults was characterized
by IL-17, IL-22, IFN-\selectlanguage{greek}γ, \selectlanguage{english}and IL-10, whereas the AD patients' T cells
lacked IL-17 production and released only low amounts of IL-22, IFN-\selectlanguage{greek}γ,
\selectlanguage{english}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: Esp elicits type 2-biased response in AD
patients. This suggests that S. epidermidis can aggravate AD through the
allergenic properties of Esp.%
\end{abstract}%



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