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S100-Alarmins are Crucial Host Factors for the Postnatal Development of Gut Homeostasis

58 Pages Posted: 7 May 2019 Publication Status: Review Complete

See all articles by Lena Völlger

Lena Völlger

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Thomas Ulas

University of Bonn, LIMES Institute, Genomics and Immunoregulation; German Center for Neurodegenerative Diseases (DZNE) - Platform for Single Cell Genomics and Epigenomics (PRECISE)

Sabine Pirr

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Anna S. Heinemann

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Thomas Vogl

University of Muenster - Institute of Immunology

Julia Pagel

University of Lubeck - Department of Pediatrics

Maike Willers

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Olga Halle

Hannover Medical School - Institute of Immunology

Sabine Schreek

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Jennifer Schöning

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Oksana Salwasser

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Yi Yu

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Beate Fehlhaber

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Peter Hombach

University of Bonn, Life and Medical Sciences Institute (LIMES), Genomics & Immunoregulation

Simon Graspeuntner

University of Lubeck - Department of Infectious Diseases and Microbiology

Katja Cloppenborg-Schmidt

University of Kiel - Institute of Experimental Medicine

Sven Künzel

Max Planck Institute for Evolutionary Biology

Danny Jonigk

Hannover Medical School - Department of Pathology

Jan Rupp

University of Lubeck - Department of Infectious Diseases and Microbiology

Gesine Hansen

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Reinhold Förster

Hannover Medical School - Institute of Immunology

John F. Baines

University of Kiel - Institute of Experimental Medicine

Christoph Härtel

University of Lubeck - Department of Pediatrics

Joachim L. Schultze

University of Bonn, LIMES Institute, Genomics and Immunoregulation; German Center for Neurodegenerative Diseases (DZNE) - Platform for Single Cell Genomics and Epigenomics (PRECISE); University of Bonn

Johannes Roth

University of Muenster - Institute of Immunology

Dorothee Viemann

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

More...

Abstract

SummaryAfter birth, the immune system experiences considerable reprogramming by interacting with the colonizing microbiota. Host factors involved in this relationship are largely unknown. Our studies in two infant cohorts and newborn mice reveal that abundant enteral S100A8/A9 trains the inflammatory and regulatory phenotype of colonic lamina propria macrophages. Neonatal S100A8/A9-alarmin deficiency results in an impaired expression of Cx3cr1, Il-10 and Tgf-β, reduced expansion of regulatory T cells, and dominant gut colonization with aerobes and facultative anaerobes, translating into a higher risk of gut dysbiosis and septic diseases preventable by one-time feeding of S100A8 at birth. Our results establish S100A8/A9 as an important host factor for developing gut homeostasis and a promising target for enteral supplementation aiming to prevent dysbiosis and associated diseases.

Keywords: Mucosal immunity, gut colonization, neonate, alarmins, S100A8, S100A9, macrophage, Regulatory T Cells, gut dysbiosis, sepsis

Suggested Citation

Völlger, Lena and Ulas, Thomas and Pirr, Sabine and Heinemann, Anna S. and Vogl, Thomas and Pagel, Julia and Willers, Maike and Halle, Olga and Schreek, Sabine and Schöning, Jennifer and Salwasser, Oksana and Yu, Yi and Fehlhaber, Beate and Hombach, Peter and Graspeuntner, Simon and Cloppenborg-Schmidt, Katja and Künzel, Sven and Jonigk, Danny and Rupp, Jan and Hansen, Gesine and Förster, Reinhold and Baines, John F. and Härtel, Christoph and Schultze, Joachim L. and Roth, Johannes and Viemann, Dorothee, S100-Alarmins are Crucial Host Factors for the Postnatal Development of Gut Homeostasis (May 4, 2019). Available at SSRN: https://ssrn.com/abstract=3382548 or http://dx.doi.org/10.2139/ssrn.3382548
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Lena Völlger

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Thomas Ulas

University of Bonn, LIMES Institute, Genomics and Immunoregulation

Bonn
Germany

German Center for Neurodegenerative Diseases (DZNE) - Platform for Single Cell Genomics and Epigenomics (PRECISE)

Bonn
Germany

Sabine Pirr

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Anna S. Heinemann

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Thomas Vogl

University of Muenster - Institute of Immunology

Germany

Julia Pagel

University of Lubeck - Department of Pediatrics ( email )

Germany

Maike Willers

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Olga Halle

Hannover Medical School - Institute of Immunology ( email )

Germany

Sabine Schreek

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Jennifer Schöning

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Oksana Salwasser

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Yi Yu

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology

Germany

Beate Fehlhaber

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Peter Hombach

University of Bonn, Life and Medical Sciences Institute (LIMES), Genomics & Immunoregulation ( email )

Bonn
Germany

Simon Graspeuntner

University of Lubeck - Department of Infectious Diseases and Microbiology ( email )

Germany

Katja Cloppenborg-Schmidt

University of Kiel - Institute of Experimental Medicine ( email )

Germany

Sven Künzel

Max Planck Institute for Evolutionary Biology ( email )

August-Thienemann-Straße 2
Plön, 24306
Germany

Danny Jonigk

Hannover Medical School - Department of Pathology ( email )

Germany

Jan Rupp

University of Lubeck - Department of Infectious Diseases and Microbiology ( email )

Germany

Gesine Hansen

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

Reinhold Förster

Hannover Medical School - Institute of Immunology ( email )

Germany

John F. Baines

University of Kiel - Institute of Experimental Medicine ( email )

Germany

Christoph Härtel

University of Lubeck - Department of Pediatrics ( email )

Germany

Joachim L. Schultze

University of Bonn, LIMES Institute, Genomics and Immunoregulation ( email )

Bonn
Germany

German Center for Neurodegenerative Diseases (DZNE) - Platform for Single Cell Genomics and Epigenomics (PRECISE) ( email )

Bonn
Germany

University of Bonn ( email )

Regina-Pacis-Weg 3
Postfach 2220
Bonn, D-53012
Germany

Johannes Roth

University of Muenster - Institute of Immunology

Germany

Dorothee Viemann (Contact Author)

Hannover Medical School - Department of Pediatric Pneumology, Allergology and Neonatology ( email )

Germany

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