Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells

Innate lymphoid cells (ILCs) are a group of hematopoietic cells devoid of antigen receptors that have important functions in lymphoid organogenesis, in the defense against extracellular pathogens, and in the maintenance of the epithelial barrier. Three distinct groups of ILCs have been identified on the basis of phenotypic and functional criteria and termed ILCs1, ILCs2, and ILCs3. Specifically, ILCs1 express the transcription factor T-bet and secrete T helper type-1- (Th1-) related cytokines, ILCs2 are dependent on the transcription factor RORαand express Gata-3 and the chemokine receptor homologous molecule (CRTH2) and produce Th2-related cytokines, and ILCs3 express the transcription factor RORγt and synthesize interleukin- (IL-) 17, IL-22, and, under specific stimuli, interferon-γ. ILCs represent a relatively small population in the gut, but accumulating evidence suggests that these cells could play a decisive role in orchestrating both protective and detrimental immune responses. In this review, we will summarize the present knowledge on the distribution of ILCs in the intestinal mucosa, with particular focus on their role in the control of both infections and effector cytokine response in immune-mediated pathologies.

Download Full-text

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

Scientific Reports ◽

10.1038/s41598-019-51690-z ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Sonja Koch ◽

Lisa Knipfer ◽

Julia Kölle ◽

Hooman Mirzakhani ◽

Anna Graser ◽

...

Keyword(s):

T Cells ◽

Transcription Factor ◽

Peripheral Blood ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Mucus Production ◽

Interacting Protein ◽

Targeted Deletion ◽

Airway Pathology ◽

Group 2

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.

Download Full-text