Dataset Information

Identification of the novel FOXP3-dependent T_reg cell transcription factor MEOX1 by high-dimensional analysis of human CD4⁺ T cells.

ABSTRACT: CD4⁺ T cells play a central role in the adaptive immune response through their capacity to activate, support and control other immune cells. Although these cells have become the focus of intense research, a comprehensive understanding of the underlying regulatory networks that orchestrate CD4⁺ T cell function and activation is still incomplete. Here, we analyzed a large transcriptomic dataset consisting of 48 different human CD4⁺ T cell conditions. By performing reverse network engineering, we identified six common denominators of CD4⁺ T cell functionality (CREB1, E2F3, AHR, STAT1, NFAT5 and NFATC3). Moreover, we also analyzed condition-specific genes which led us to the identification of the transcription factor MEOX1 in T_reg cells. Expression of MEOX1 was comparable to FOXP3 in T_reg cells and can be upregulated by IL-2. Epigenetic analyses revealed a permissive epigenetic landscape for MEOX1 solely in T_reg cells. Knockdown of MEOX1 in T_reg cells revealed a profound impact on downstream gene expression programs and T_reg cell suppressive capacity. These findings in the context of CD4⁺ T cells contribute to a better understanding of the transcriptional networks and biological mechanisms controlling CD4⁺ T cell functionality, which opens new avenues for future therapeutic strategies.

SUBMITTER: Baßler K

PROVIDER: S-EPMC10407399 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells.

Baßler Kevin K Schmidleithner Lisa L Shakiba Mehrnoush Hadaddzadeh MH Elmzzahi Tarek T Köhne Maren M Floess Stefan S Scholz Rebekka R Ohkura Naganari N Sadlon Timothy T Klee Kathrin K Neubauer Anna A Sakaguchi Shimon S Barry Simon C SC Huehn Jochen J Bonaguro Lorenzo L Ulas Thomas T Beyer Marc M

Frontiers in immunology 20230725

CD4+ T cells play a central role in the adaptive immune response through their capacity to activate, support and control other immune cells. Although these cells have become the focus of intense research, a comprehensive understanding of the underlying regulatory networks that orchestrate CD4+ T cell function and activation is still incomplete. Here, we analyzed a large transcriptomic dataset consisting of 48 different human CD4+ T cell conditions. By performing ...[more]

PMID: 37559728

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Project description:BackgroundRegulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4+CD25+Foxp3+ in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4+ICOS+Foxp3+ T cells in resistance/susceptibility during malaria parasite is explored in this study.Methods5 × 105 red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay.ResultsThin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4+ ICOS+ T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4+ICOS+FoxP3+ Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite.ConclusionTaken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved.

Dataset Information

Identification of the novel FOXP3-dependent T_reg cell transcription factor MEOX1 by high-dimensional analysis of human CD4⁺ T cells.

Publications

Identification of the novel FOXP3-dependent T<sub>reg</sub> cell transcription factor MEOX1 by high-dimensional analysis of human CD4<sup>+</sup> T cells.

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