Targeted deletion of NFAT-Interacting-Protein-(NIP) 45 resolves experimental asthma by inhibiting Innate Lymphoid Cells group 2 (ILC2)

Koch S, Knipfer L, Kölle J, Mirzakhani H, Graser A, Zimmermann T, Kiefer A, Melichar VO, Rascher W, Papadopoulos NG, Rieker R, Raby BA, Weiss ST, Wirtz S, Finotto S (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 9

Article Number: 15695

Journal Issue: 1

DOI: 10.1038/s41598-019-51690-z

Abstract

Here we investigated the role of NFAT-interacting protein (NIP)-45, an Interleukin (IL)-4 inducing Transcription Factor, and its impact on the differentiation of Group 2 Innate -Lymphoid -Cells (ILC2s) in the pathogenesis of asthma. NIP45, a transcription factor regulating NFATc1 activity, mRNA was found to be induced in the Peripheral Blood mononuclear cells (PMBCs) of asthmatic pre-school children with allergies and in the peripheral blood CD4+ T cells from adult asthmatic patients. In PBMCs of asthmatic and control children, NIP45 mRNA directly correlated with NFATc1 but not with T-bet. Targeted deletion of NIP45 in mice resulted in a protective phenotype in experimental asthma with reduced airway mucus production, airway hyperresponsiveness and eosinophils. This phenotype was reversed by intranasal delivery of recombinant r-IL-33. Consistently, ILC2s and not GATA3+ CD4+ T-cells were decreased in the lungs of asthmatic NIP45−/− mice. Reduced cell number spleen ILC2s could be differentiated from NIP45−/− as compared to wild-type mice after in vivo injection of a microcircle-DNA vector expressing IL-25 and decreased cytokines and ILC2 markers in ILC2 differentiated from the bone marrow of NIP45−/− mice. NIP45 thus emerges as a new therapeutic target for the resolution of the airway pathology, down-regulation of ILC2s and mucus production in asthma.

Authors with CRIS profile

Sonja Koch Department of Molecular Pneumology Lisa Knipfer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Julia Kölle Department of Molecular Pneumology Anna Graser Department of Molecular Pneumology Theodor Zimmermann Medizinische Fakultät Alexander Kiefer Lehrstuhl für Klinische Nuklearmedizin Wolfgang Rascher Department of Paediatrics and Adolescent Medicine Ralf Rieker Institute of Pathology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Susetta Neurath-Finotto Department of Molecular Pneumology

Involved external institutions

Brigham and Women's Hospital (BWH) US United States (USA) (US) National and Kapodistrian University of Athens GR Greece (GR)

How to cite

APA:

Koch, S., Knipfer, L., Kölle, J., Mirzakhani, H., Graser, A., Zimmermann, T.,... Finotto, S. (2019). Targeted deletion of NFAT-Interacting-Protein-(NIP) 45 resolves experimental asthma by inhibiting Innate Lymphoid Cells group 2 (ILC2). Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-51690-z

MLA:

Koch, Sonja, et al. "Targeted deletion of NFAT-Interacting-Protein-(NIP) 45 resolves experimental asthma by inhibiting Innate Lymphoid Cells group 2 (ILC2)." Scientific Reports 9.1 (2019).

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