The Discovery of Chicken Foxp3 Demands Redefinition of Avian Regulatory T Cells

Burkhardt, N.; Elleder, Daniel; Schusser, Benjamin; Krchlíková, Veronika; Göbel, Thomas; Härtle, Sonja; Kaspers, Bernd

doi:10.4049/jimmunol.2000301

Cited by 20 publications

(16 citation statements)

References 59 publications

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“…Foxp3 is a hallmark molecule of Treg cells, but a chicken ortholog was only identified in 2022, and its function is unclear [ 33 , 34 ]. Avian Treg cells are usually defined as CD4 + CD25 + cells [ 35 ]; here, we used CD3 + CD4 + CD25 + as the standard for isolation and identification of avian Treg cells ( Figure 3 B).…”

Section: Resultsmentioning

confidence: 99%

Clostridium butyricum Can Promote Bone Development by Regulating Lymphocyte Function in Layer Pullets

Song

Hao

Sun

2023

IJMS

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Bone health problems are a serious threat to laying hens; microbiome-based therapies, which are harmless and inexpensive, may be an effective solution for bone health problems. Here, we examined the impacts of supplementation with Clostridium butyricum (CB) on bone and immune homeostasis in pullets. The results of in vivo experiments showed that feeding the pullets CB was beneficial to the development of the tibia and upregulated the levels of the bone formation marker alkaline phosphatase and the marker gene runt-related transcription factor 2 (RUNX2). For the immune system, CB treatment significantly upregulated IL-10 expression and significantly increased the proportion of T regulatory (Treg) cells in the spleen and peripheral blood lymphocytes. In the in vitro test, adding CB culture supernatant or butyrate to the osteoblast culture system showed no significant effects on osteoblast bone formation, while adding lymphocyte culture supernatant significantly promoted bone formation. In addition, culture supernatants supplemented with treated lymphocytes (pretreated with CB culture supernatants) stimulated higher levels of bone formation. In sum, the addition of CB improved bone health by modulating cytokine expression and the ratio of Treg cells in the immune systems of layer pullets. Additionally, in vitro CB could promote the bone formation of laying hen osteoblasts through the mediation of lymphocytes.

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Section: Resultsmentioning

confidence: 99%

Clostridium butyricum Can Promote Bone Development by Regulating Lymphocyte Function in Layer Pullets

Song

Hao

Sun

2023

IJMS

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“…To identify LAT genes in avian genomes, we used similar approach as in our previous searches for avian GC-rich ‘hidden’ genes [ 18 – 20 ]. We performed homology-based searches of the SRA datasets in NCBI (mostly represented by Illumina RNA-seq data) to assemble full coding sequences of LAT in ten bird species including chicken.…”

Section: Resultsmentioning

confidence: 99%

Identification of GC-rich LAT genes in birds

et al. 2023

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Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling.

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“…Moreover, the significantly lower expression of FoxP3 and TGFβ in TCR Cβ -/- chickens matches the absence of CD4 + T cells and also indicates the loss of T reg cells. IL-10 and TGFβ secreted by T reg cells have anti-inflammatory and immunosuppressive effects, inhibiting the activation and function of CD8 + T cells and monocytes, which are involved in the cytotoxic response (7). In the TCR Cβ -/- chicken the regulation of cytotoxic activity of γδ T cells and macrophages is therefore disrupted.…”

Section: Discussionmentioning

confidence: 99%

“…The CD4 + αβ T cells are activated through antigens bound to major histocompatibility complex (MHC) II molecules, leading to a humoral immune response against pathogens (6). Regulatory T cells (T regs ), typically expressing CD4 + CD25 + and the transcription factor FoxP3 + (7), play an important role in maintaining immune tolerance (8). CD8 + αβ T cells recognize peptides presented by MHC I molecules (9) and show cytotoxic activity (6).…”

Section: Introductionmentioning

confidence: 99%

Knockout of αβ but not γδ T cells in chickens is associated with high cytotoxicity and deficiency of regulatory and helper T cells

Heyl

Klinger

Aumann

et al. 2023

Preprint

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The availability of genetically modified mice has facilitated the study of mammalian T cells. No model has yet been developed to study these cells in chicken, an important livestock species with a high availability of gd T cells. To investigate the role of gd and ab T cell populations in birds, we generated chickens lacking these T cell populations. This was achieved by genomic deletion of the constant region of the T cell receptor g or b chain, leading to a complete loss of either gd or ab T cells. Our results show that a deletion of ab T cells but not gd T cells resulted in a severe phenotype in knockout chickens. The ab T cell knockout chickens exhibited granulomas associated with inflammation of the spleen and the proventriculus. Immunophenotyping of ab T cell knockout chickens revealed a significant increase in monocytes and the absence of CD4+ T cells and FoxP3+ regulatory T cells compared to wild type chickens. In addition, we observed a significant decrease in immunoglobulins, B lymphocytes, and changes in the bursa morphology. Our data reveal the consequences of T cell knockouts in chickens and provide new insights into their function in vertebrates.

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The Discovery of Chicken Foxp3 Demands Redefinition of Avian Regulatory T Cells

Cited by 20 publications

References 59 publications

Clostridium butyricum Can Promote Bone Development by Regulating Lymphocyte Function in Layer Pullets

Clostridium butyricum Can Promote Bone Development by Regulating Lymphocyte Function in Layer Pullets

Identification of GC-rich LAT genes in birds

Knockout of αβ but not γδ T cells in chickens is associated with high cytotoxicity and deficiency of regulatory and helper T cells

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