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

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.

scholarly journals Cell type–specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Hiroyuki Hosokawa ◽  
Maile Romero-Wolf ◽  
Qi Yang ◽  
Yasutaka Motomura ◽  
Ditsa Levanon ◽  
...  
Keyword(s):  
T Cells ◽  
Target Genes ◽  
Cell Types ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Cell Type ◽  
Distal Enhancer ◽  
Distinct Cell Type ◽  
Cell Type Specific ◽  
Group 2

The zinc finger transcription factor, Bcl11b, is expressed in T cells and group 2 innate lymphoid cells (ILC2s) among hematopoietic cells. In early T-lineage cells, Bcl11b directly binds and represses the gene encoding the E protein antagonist, Id2, preventing pro-T cells from adopting innate-like fates. In contrast, ILC2s co-express both Bcl11b and Id2. To address this contradiction, we have directly compared Bcl11b action mechanisms in pro-T cells and ILC2s. We found that Bcl11b binding to regions across the genome shows distinct cell type–specific motif preferences. Bcl11b occupies functionally different sites in lineage-specific patterns and controls totally different sets of target genes in these cell types. In addition, Bcl11b bears cell type–specific post-translational modifications and organizes different cell type–specific protein complexes. However, both cell types use the same distal enhancer region to control timing of Bcl11b activation. Therefore, although pro-T cells and ILC2s both need Bcl11b for optimal development and function, Bcl11b works substantially differently in these two cell types.

scholarly journals The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo

2020 ◽  
Vol 18 (1) ◽  
pp. 230-242 ◽  
Author(s):  
Lei Zhang ◽  
Yuanlin Ying ◽  
Shuqiu Chen ◽  
Preston R. Arnold ◽  
Fafa Tian ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2 ◽  
Immune Pathology

scholarly journals Increased expression of Fas on group 2 and 3 innate lymphoid cells is associated with an interferon signature in systemic lupus erythematosus and Sjögren’s syndrome

Rheumatology ◽  
2019 ◽  
Vol 58 (10) ◽  
pp. 1740-1745 ◽  
Author(s):  
Sofie L M Blokland ◽  
Lucas L van den Hoogen ◽  
Emmerik F A Leijten ◽  
Sarita A Y Hartgring ◽  
Ruth Fritsch ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Peripheral Blood ◽  
Innate Lymphoid Cells ◽  
Sjogren's Syndrome ◽  
Plasmacytoid Dendritic Cells ◽  
Lymphoid Cells ◽  
Type I ◽  
Healthy Controls ◽  
Type I Ifn ◽  
Group 2

Abstract Objective The role of innate lymphoid cells (ILCs) in the pathophysiology of rheumatic diseases is emerging. Evidence from animal studies implicate type I IFN, produced by plasmacytoid dendritic cells, to be involved in regulating the survival of group 2 and group 3 ILCs (ILC2s and ILC3s) via the upregulation of Fas (CD95) expression. For the first time, we explored the frequency and phenotype of circulating ILCs in SLE and primary Sjögren’s syndrome (pSS) in relationship to the IFN signature. Methods Frequencies and phenotypes of ILC subsets and plasmacytoid dendritic cells were assessed by flow cytometry in peripheral blood of patients with SLE (n = 20), pSS (n = 20) and healthy controls (n = 17). Patients were stratified by the presence or absence of an IFN signature as assessed by RT-qPCR on circulating mononuclear cells. Results ILC1 frequencies were increased in peripheral blood of patients with SLE as compared with healthy controls and correlate with disease activity in pSS patients. Overall, the frequencies of ILC2s or ILC3s did not differ between patients with SLE, pSS and healthy controls. However, patients with a high type I IFN signature expressed elevated levels of Fas on ILC2s and ILC3s, which coincided with decreased frequencies of these cells in blood. Conclusion The presence of a type I IFN signature is related to Fas expression and frequencies of circulating ILC2s and ILC3s in patients with SLE and pSS, potentially altering the homeostatic balance of ILCs.

scholarly journals Increased group 2 innate lymphoid cells in peripheral blood of adults with mastocytosis

2020 ◽  
Author(s):  
Esmee K. van der Ploeg ◽  
Maud A.W. Hermans ◽  
Vincent H.J. van der Velden ◽  
Willem A. Dik ◽  
Paul L.A. van Daele ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

scholarly journals MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4+ T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion

Immunity ◽  
2014 ◽  
Vol 41 (2) ◽  
pp. 283-295 ◽  
Author(s):  
Christopher J. Oliphant ◽  
You Yi Hwang ◽  
Jennifer A. Walker ◽  
Maryam Salimi ◽  
See Heng Wong ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Parasitic Helminth ◽  
Type 2 Immunity ◽  
Group 2

scholarly journals Enforced Expression of Gata3 in T Cells and Group 2 Innate Lymphoid Cells Increases Susceptibility to Allergic Airway Inflammation in Mice

2014 ◽  
Vol 192 (4) ◽  
pp. 1385-1394 ◽  
Author(s):  
Alex KleinJan ◽  
Roel G. J. Klein Wolterink ◽  
Yelvi Levani ◽  
Marjolein J. W. de Bruijn ◽  
Henk C. Hoogsteden ◽  
...  
Keyword(s):  
T Cells ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

T Cells and Group 2 Innate Lymphoid Cells 2

2022 ◽  
pp. 37-46
Author(s):  
Atsushi Kato ◽  
Robert P. Schleimer
Keyword(s):  
T Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2
Sign in / Sign up

Export Citation Format

Share Document