\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{The protective farm effect against allergies in a holoBLG based FSMP
(food for specific medical purposes)-lozenge confers immune resilience
in BALB/c mice}



\author[1]{Sheriene Afify}%
\author[1]{Andreas Regner}%
\author[2]{Luis Pacios}%
\author[3]{Bart Blokhuis}%
\author[4]{sebastian jensen}%
\author[5]{Frank Redegeld}%
\author[1]{Isabella Pali-Schöll}%
\author[1]{Karin Hufnagl}%
\author[1]{Rodolfo Bianchini}%
\author[6]{Sonja Guethoff}%
\author[7]{Matthias Kramer}%
\author[8]{Alessandro Fiocchi}%
\author[9]{Zdenek Dvorak}%
\author[1]{Erika Jensen-Jarolim}%
\author[1]{Franziska Roth-Walter}%
\affil[1]{University of Veterinary Medicine Vienna Messerli-Research-Institute}%
\affil[2]{E.T.S. Ingenieros de Montes, UPM}%
\affil[3]{Universiteit Utrecht}%
\affil[4]{Medical University of Vienna Center of Pathophysiology Infectiology and Immunology}%
\affil[5]{Utrecht University}%
\affil[6]{Bencard Allergie GmbH}%
\affil[7]{Allergy Therapeutics Plc}%
\affil[8]{Bambino Gesu Pediatric Hospital}%
\affil[9]{Palacky University Olomouc Faculty of Science}%


\vspace{-1em}



  
  \date{June 10, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background: We previously proposed the whey protein beta-lactoglobulin
(BLG) loaded with iron-siderophore complexes as the active principle in
the farm protective effect against allergies. A lozenge as food for
specific medical purposes (FSMP) was formulated to assess its
therapeutical efficacy in BALB/c mice and in-vitro experiments. Methods:
Binding of iron-catechin into BLG was confirmed by spectroscopy and
docking calculations. Serum IgE binding of children allergic to milk, or
tolerating milk, was assessed to loaded (holo-) versus empty (apo-) BLG
and for human mast cell degranulation. BLG and Bet v 1 double-sensitized
mice were orally treated with the lozenge or placebo, and
immunologically analysed after systemic allergen challenge. Human PBMCs
of pollen allergic subjects were flow cytometrically assessed after
stimulation with holoBLG in conjugation with catechin-iron complexes as
ligands in a dietary supplement or with the apoBLG. Results: One major
IgE- and T cell epitope were masked by catechin-iron complexes, which
impaired IgE binding of milk allergic children and degranulation of mast
cells. In mice, only supplementation with the lozenge reduced clinical
reactivity to BLG and Bet v 1, promoted Tregs, and suppressed antigen
presentation. In allergic subjects, stimulation of PBMCs with holoBLG
led to a significant increase of intracellular iron in circulating CD14+
cells with significantly lower expression of HLADR and CD86 compared to
their stimulation with apoBLG. Conclusion: The FSMP lozenge targeted
antigen presenting cells and dampened immune activation in human immune
cells and allergic mice in an antigen nonspecific manner, thereby
conferring immune resilience against allergic symptoms.%
\end{abstract}%



\sloppy




\selectlanguage{english}
\FloatBarrier
\end{document}

