Neonatal T helper 17 responses are skewed towards an immunoregulatory interleukin-22 phenotype
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ABSTRACT:
PROVIDER: PRJNA558982 | ENA |
REPOSITORIES: ENA
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Project description:Newborns are frequently affected by mucocutaneous candidiasis. Th17 cells essentially limit mucosal invasion by commensal Candida spp. Here, we sought to understand the molecular basis for the developmental lack of Th17 cell responses in circulating blood neonatal T cells. Naive cord blood CD4 T cells stimulated in Th17-differentiating conditions inherently produced high levels of the interleukin-22 immunoregulatory cytokine, particularly in the presence of neonatal antigen-presenting cells. A genome-wide transcriptome analysis comparing neonatal and adult naïve CD4 T cells ex vivo revealed major developmental differences in gene networks regulating Small Drosophila Mothers Against Decapentaplegic (SMAD) and Signal Transducer and Activator of Transcription 3 (STAT3) signaling. These changes were functionally validated by experiments showing that the requirement for TGF-β in human Th17 cell differentiation is age-dependent. Moreover, STAT3 activity was profoundly diminished while overexpression of the STAT3 gene restored Th17 cell differentiation capacity in neonatal T cells. These data reveal that Th17 cell responses are developmentally regulated at the gene expression level in human neonates. These developmental changes may protect newborns against pathological Th17 cell responses, at the same time increasing their susceptibility to mucocutaneous candidiasis.
| S-EPMC8126652 | biostudies-literature
Project description:We report broad developmental differences in gene expression profiles between neonatal (term) and adult naive CD4 T cells, resulting in non-stereotypic Th17 differentiation responses to TGF-beta.
2020-12-31 | GSE135467 | GEO
Project description:Recently, three-dimensional small intestinal organoids (enteroids) have been developed from cultures of intestinal stem cells which differentiate in vitro to generate all the differentiated epithelial cell types associated with the intestine and mimic the structural properties of the intestine observed in vivo. Small-molecule drug treatment can skew organoid epithelial cell differentiation towards particular lineages, and these skewed enteroids may provide useful tools to study specific epithelial cell populations, such as goblet and Paneth cells. However, the use and characterisation of enteroid models has not yet been fully explored, such that the extent to which differentiated epithelial cell populations in these skewed enteroids represent their in vivo counterparts is not fully understood. In this study, we have performed label-free quantitative proteomics to determine whether skewing murine enteroid cultures towards the goblet or Paneth cell lineages results in changes in abundance of proteins associated with these cell lineages in vivo. Our data confirm that skewed enteroids recapitulate important features of the in vivo gut environment, confirming that they can serve as useful models for the investigation of normal and disease processes in the intestine. Furthermore, by comparison of our mass spectrometry data with histology data contained within the Human Protein Atlas, we identify putative novel markers for goblet and Paneth cells.
2019-01-11 | PXD005006 | Pride
Project description:Cytokine receptor modulation by interleukin-2 broadly regulates T helper cell lineage differentiation
| PRJNA137397 | ENA
Project description:Mycosis Fungoides (MF) is typically characterized by a mature CD4+ memory T-cell phenotype, and regarded as a helper T-cell (Th)2-skewed disease. Here, using skin samples from MF (n=21), healthy volunteers (n=17), atopic dermatitis (n=17), and psoriasis (n=9), we performed RT-PCR to show highest interleukin (IL)-32 mRNA expression in MF compared to benign inflammatory diseases, and its increasing expression with disease progression. By immunohistochemistry and immunofluorescence, we confirmed IL-32 protein expression by numerous CD3+CD4+ T-cells and some epidermotropic T-cells in MF lesions. IL-32 is expressed by MyLa cells (MF cell line) and promoted their proliferation and viability in a dose-dependent fashion. IL-32-treated MyLa and HH cells (CTCL cell line) showed upregulation of cell proliferation and survival genes. Of major 'polar' T-cell cytokines, only IFN-γ mRNA increases with MF progression and positively correlates with IL-32 mRNA expression levels. Th2 cytokines do not show consistent increases with MF progression nor positive correlation with IL-32 mRNA expression levels. Furthermore, by flow cytometry, IL-32 production by circulating activated T-cells in healthy individulas was found in IFN-γ+ and IFN-γ- cells but not in IL-4+ or IL-13+ cells. In conclusion, we identified IL-32+ cells as likely tumor cells in MF, and clearly showed that IL-32 mRNA expression levels increase with MF progression. We found that IL-32 mRNA expression levels in MF are significantly higher than those in other skin diseases, and that some IL-32+ T-cells are independent from defined Th subsets. Thus IL-32 may play a unique role in MF progression as an autocrine cytokine.
2014-12-31 | GSE58033 | GEO
Project description:Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. Furthermore, genome wide occupancy and overexpression studies in Th17 cells revealed that Blimp-1 co-localized with transcription factors RORγt, STAT-3 and p300 at the Il23r, Il17a/f and Csf2 cytokine loci to enhance their expression. Blimp-1 also directly bound to and repressed cytokine loci Il2 and Bcl6. Taken together, our results demonstrate that Blimp-1 is an essential transcription factor downstream of IL-23 that acts in concert with RORγt to activate the Th17 inflammatory program. Genome-wide binding analysis of Blimp1 from in vitro generated T effector and regulatory cells
2016-06-15 | E-GEOD-75724 | biostudies-arrayexpress
Project description:H3K4me1 Mint-ChIP-seq on T-helper 1 cell male adult (35 years) treated with 1 ?g/mL Interleukin-4 antibody , 30 ng/mL Interleukin-12 subunit alpha , 30 ng/mL Interleukin-12 subunit beta For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-11-04 | GSE187901 | GEO
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2021-11-04 | GSE187818 | GEO
Project description:H3K4me3 Mint-ChIP-seq on T-helper 1 cell male adult (35 years) treated with 1 ?g/mL Interleukin-4 antibody , 30 ng/mL Interleukin-12 subunit alpha , 30 ng/mL Interleukin-12 subunit beta For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-11-04 | GSE187764 | GEO
Project description:H3K36me3 Mint-ChIP-seq on T-helper 1 cell male adult (35 years) treated with 1 ?g/mL Interleukin-4 antibody , 30 ng/mL Interleukin-12 subunit alpha , 30 ng/mL Interleukin-12 subunit beta For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-11-04 | GSE187096 | GEO