Dataset Information

Insulin-like growth factors alter the transcriptional identity of Th17 cells

ABSTRACT: Th17s treated with insulin-like growth factors express higher levels of genes associated with activation, Th17 identity, peripheral maturation and effector function, while control Th17s are relatively enriched for genes associated with Treg identity and function.

ORGANISM(S): Mus musculus

PROVIDER: GSE114733 | GEO | 2020/08/12

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the interleukin-4 receptor alpha chain (IL-4RÎ±-R576) biases induced Treg (iTreg) cells towards a T helper 17 (TH17) cell fate. This skewing reflects the recruitment by IL-4RÎ±-R576 of the adaptor protein growth factor receptor-bound protein 2 (GRB2), which drives IL-17 expression by an extracellular signal-regulated kinase-, IL-6- and STAT3-dependent mechanism. We showed that the IL-4RÎ±-R576 mutation elicits TH17 airway responses in vivo, in a house dust mite (HDM)- or ovalbumin (OVA)-driven model of airway inflammation in the mice carry the IL-4RÎ±-R576 mutation (Il4raR576 mice). Treg cell-specific deletion of genes encoding IL-6RÎ± or the master TH17 cell regulator Retinoid-related Orphan Receptor Î³t (RORÎ³t), but not IL-4 and IL-13, protected mice against exacerbated airway inflammation induced by IL-4RÎ±--576. Analysis of lung tissue Treg cells revealed that the expression of IL-17 and the TH17 cell-associated chemokine receptor CCR6 was largely overlapping and highly enriched in Treg and conventional T (Tconv) cells of allergen-treated Il4raR576 mice. To further characterize the subset of IL-17 producing Foxp3+ Treg in the lung of OVA-treated mice we utilized CCR6 as a marker of Treg cells committed towards the TH17 cell lineage to examine their functional, epigenetic and transcriptional profiles. CCR6+Foxp3EGFP+ Treg cells isolated from OVA-sensitized and challenged Il4raR576 mice, by FACS (Fluorescence Activated Cell Sorting) exhibited decreased methylation of the Foxp3 CNS2 locus comparing to CCR6âFoxp3EGFP+ Treg cells from same animals, indicative of decreased stability. They also exhibited profoundly decreased suppressive function as compared to CCR6â WT and CCR6â Il4raR576 counterparts. Transcriptional profiling of CCR6+Foxp3EGFP+ Treg cells revealed increased relative expression in CCR6+ Il4raR576 Treg cells of genes associated with a TH17 cell signature, including Rorc, Ccr6, Il23r, Il17a, Il17f, Il1r1, Nr1d1, Cstl, and Ahr comparing to CCR6âFoxp3EGFP+ Treg cells from same animals. Three CCR6+Foxp3EGFP+ Il4raR576 replicates and four CCR6âFoxp3EGFP+ Il4raR576 Treg replicates (controls) were sampled

Dataset Information

Insulin-like growth factors alter the transcriptional identity of Th17 cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets