Τίτλος:
Targeted deletion of NFAT-Interacting-Protein-(NIP) 45 resolves experimental asthma by inhibiting Innate Lymphoid Cells group 2 (ILC2)
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2019, The Author(s).
Συγγραφείς:
Koch, S.
Knipfer, L.
Kölle, J.
Mirzakhani, H.
Graser, A.
Zimmermann, T.
Kiefer, A.
Melichar, V.O.
Rascher, W.
Papadopoulos, N.G.
Rieker, R.J.
Raby, B.A.
Weiss, S.T.
Wirtz, S.
Finotto, S.
Περιοδικό:
Scientific Reports
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
carrier protein; interleukin 33; NFATC1 protein, human; nuclear factor of activated T cells, cytoplasmic-2 interacting protein, human; T box transcription factor; T-box transcription factor TBX21; transcription factor NFAT, animal; asthma; child; disease model; female; genetics; human; immunology; innate immunity; knockout mouse; lung; lymphocyte; male; metabolism; mononuclear cell; mouse; mucus; pathology; preschool child; respiratory tract allergy, Animals; Asthma; Carrier Proteins; Child; Child, Preschool; Disease Models, Animal; Female; Humans; Immunity, Innate; Interleukin-33; Leukocytes, Mononuclear; Lung; Lymphocytes; Male; Mice; Mice, Knockout; Mucus; NFATC Transcription Factors; Respiratory Hypersensitivity; T-Box Domain Proteins
DOI:
10.1038/s41598-019-51690-z
