Transcriptomics,Genomics

Dataset Information

40

Gene expression analysis of ex-Foxp3 Th2 cells during Heligmosomoides polygyrus infection


ABSTRACT: Gene expression of Treg cells that have lost Foxp3 expression and acquired Il4 expression following adoptive transfer into T-cell deficient mice (HpTR-IL-4gfp+), cmpared to conventional Treg cells isolated from H. polygyrus-infected wild-type mice (HpTR) and Th2 cells generated from naïve T cells following adoptive transfer into H. polygyrus-infected T-cell deficient mice (nT-IL-4gfp+). Immunity to intestinal helminth infections requires the rapid activation of T helper 2 (Th2) cells. However, simultaneous expansion of regulatory CD4+Foxp3+ T (Treg) cells impedes protective responses, resulting in chronic infections. The ratio between regulatory and effector T cells can therefore determine the outcome of infection. The re-differentiation of Treg into T helper (Th) cells has been identified in hyper-inflammatory diseases. In this study, we asked whether ex-Treg Th2 cells develop and contribute to type 2 immunity. Using multi-gene reporter and fate-reporter systems we demonstrate that a significant proportion of Th2 cells derive from Foxp3+ cells following Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus. Through selective deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting Treg cells into Th2 cells could concomitantly enhance Th2 cells and limit Treg-mediated suppression.   Overall design: Naïve T cells were FACS-sorted from naive wild-type mice. HpTR cells were FACS-sorted from H. polygyrus-infected mice. HpTR cells and nT cells were transferred to T-cell deficient mice infected with H. polygyrus. IL-4gfp-expressing cells were FACS-sorted from HpTR (HpTR-IL-4gfp+) or nT (nT-IL-4gfp+) recipients. 3 biological samples were obtained from 3 independent experiments for each sample group.

INSTRUMENT(S): [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

SUBMITTER: Victoria S Pelly  

PROVIDER: GSE98518 | GEO | 2017-05-04

SECONDARY ACCESSION(S): PRJNA385331

REPOSITORIES: GEO

altmetric image

Publications

Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths.

Pelly Victoria S VS   Coomes Stephanie M SM   Kannan Yashaswini Y   Gialitakis Manolis M   Entwistle Lewis J LJ   Perez-Lloret Jimena J   Czieso Stephanie S   Okoye Isobel S IS   Rückerl Dominik D   Allen Judith E JE   Brombacher Frank F   Wilson Mark S MS  

The Journal of experimental medicine 20170515 6


Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion of CD4+Foxp3+ regulatory T cells (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between T reg and effector T cells can therefore determine the outcome of infection. The redifferentiation of T reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we asked whether ex-T reg Th2 cells deve  ...[more]

Similar Datasets

2011-12-14 | E-GEOD-26190 | ArrayExpress
| GSE26190 | GEO
2017-04-19 | PXD006251 | Pride
2016-04-07 | E-GEOD-45976 | ArrayExpress
| PRJNA385331 | ENA
| GSE121764 | GEO
2008-06-13 | E-GEOD-4179 | ArrayExpress
| GSE106463 | GEO
2013-08-31 | E-GEOD-49380 | ArrayExpress
2010-03-31 | GSE17580 | GEO