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Evolutionary transition from degenerate to non-redundant cytokine signaling networks supporting intrathymic T cell development

ABSTRACT: Evolutionary transition from degenerate to non-redundant cytokine signaling networks supporting intrathymic T cell development

PROVIDER: PRJNA561756 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10017647_1.fastq.gz	Fastqsanger.gz
	SRR10017647_2.fastq.gz	Fastqsanger.gz
	SRR10017648_1.fastq.gz	Fastqsanger.gz
	SRR10017648_2.fastq.gz	Fastqsanger.gz
	SRR10017649_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Evolutionary transition from degenerate to non-redundant cytokine signaling networks supporting intrathymic T cell development

Project description:In mammals, T cell development in the thymus is critically dependent on the presence of the IL7 cytokine. Here, we describe the identification of the zebrafish ortholog of mammalian IL7, based on chromosomal localization, expression patterns, and deduced protein sequence. To examine the biological role of il7 in teleosts, we generated an il7 allele lacking most of its coding exons using CRISPR/Cas9-based mutagenesis. il7-deficient animals are viable, and exhibit no obvious signs of immune disorder. With respect to intrathymic T cell development, il7-deficiency is associated with only mild a reduction of thymocytes, contrasting with the much stronger reduction of T cell development il7r-deficient fish. Genetic interaction studies between il7 and crlf2(tslpr) suggest the contribution of an additional, as yet unidentified cytokine(s) to intrathymic T cell development. Such activities were also ascertained for other cytokines, such as il2 and il15, collectively indicating that, in contrast to the situation in mammals, T cell development in the thymus of teleosts is driven by a degenerate multi-component network of gc cytokines. This network configuration thus explains why deficiencies of single components have little detrimental effect. By contrast, the dependence on a single cytokine in the mammalian thymus has catastrophic consequences in case of congenital deficiencies in genes affecting the IL7 signaling pathway. We speculate that the transition from a degenerate to a non-redundant cytokine network supporting intrathymic T cell development emerged as the consequence of repurposing evolutionary ancient constitutive cytokine pathways for regulatory functions in the mammalian peripheral immune system.

2020-01-08 | GSE136250 | GEO

Evolutionary transition from degenerate to nonredundant cytokine signaling networks supporting intrathymic T cell development.

Project description:In mammals, T cell development critically depends on the IL-7 cytokine signaling pathway. Here we describe the identification of the zebrafish ortholog of mammalian IL-7 based on chromosomal localization, deduced protein sequence, and expression patterns. To examine the biological role of il7 in teleosts, we generated an il7 allele lacking most of its coding exons using CRISPR/Cas9-based mutagenesis. il7-deficient animals are viable and exhibit no obvious signs of immune disorder. With respect to intrathymic T cell development, il7 deficiency is associated with only a mild reduction of thymocyte numbers, contrasting with a more pronounced impairment of T cell development in il7r-deficient fish. Genetic interaction studies between il7 and il7r mutants, and il7 and crlf2(tslpr) mutants suggest the contribution of additional, as-yet unidentified cytokines to intrathymic T cell development. Such activities were also ascertained for other cytokines, such as il2 and il15, collectively indicating that in contrast to the situation in mammals, T cell development in the thymus of teleosts is driven by a degenerate multicomponent network of γc cytokines; this explains why deficiencies of single components have little detrimental effect. In contrast, the dependence on a single cytokine in the mammalian thymus has catastrophic consequences in cases of congenital deficiencies in genes affecting the IL-7 signaling pathway. We speculate that the transition from a degenerate to a nonredundant cytokine network supporting intrathymic T cell development emerged as a consequence of repurposing evolutionarily ancient constitutive cytokine pathways for regulatory functions in the mammalian peripheral immune system.

| S-EPMC6936713 | biostudies-literature

Functional dissection of the Csn1s2b locus identifies complex redundant and non-redundant cytokine-activated enhancers in mouse mammary gland tissue

Project description:Functional dissection of the Csn1s2b locus identifies complex redundant and non-redundant cytokine-activated enhancers in mouse mammary gland tissue

| PRJNA678955 | ENA

Intrathymic T-cell selection

Project description:Comparisons between untreated primary cells T-cell precursors from the thymus. CD69- thymocytes are from Zap70-deficent mice and are >95% CD4+CD8+. These cells fail to generate intrathymic TCR signals as a result of their lacking Zap70 molecules, and are thus representative of "preselection" CD4+CD8+ thymocytes. The CD69hi population comes from wildtype mice and is heterogeneous for CD4 and CD8 expression. These cells have been intrathymically TCR-signaled and are undergoing selection.

2010-06-10 | E-GEOD-2262 | biostudies-arrayexpress

Intrathymic T-cell selection

2005-03-07 | GSE2262 | GEO

Interferon dependent genes of intrathymic antigen presenting cells

Project description:Interferon dependent genes of intrathymic antigen presenting cells

| PRJNA792826 | ENA

Evolutionary Origin of Vertebrate Oct4/POUV Functions in Supporting Pluripotency

Project description:Evolutionary Origin of Vertebrate Oct4/POUV Functions in Supporting Pluripotency

| PRJNA758957 | ENA

Evolutionary Origin of Vertebrate Oct4/POUV Functions in Supporting Pluripotency

Project description:Evolutionary Origin of Vertebrate Oct4/POUV Functions in Supporting Pluripotency

| PRJNA623368 | ENA

Differential expression of circRNAs discriminates between different maturational stages of human intrathymic thymocytes.

Project description:Circular RNAs (circRNAs) are stable single stranded RNA molecules which form a covalently closed continuous loop. They are involved in multiple biological processes, functioning mainly through interactions with microRNAs and proteins or by the expression of specific peptides. Preliminary data exist on circRNA expression in different peripheral blood cell populations. Deregulation of circRNAs has been shown to be key in the development of T-cell acute lymphoblastic leukemia (T-ALL). However, a detailed analysis on circRNAs expression in intrathymic thymocyte populations was still missing and might be key to understanding thymus development as well as tumours arising in the lymphoblastic line. The aim of this study was to investigate whether circRNAs are differentially expressed in thymocytes at different maturational stages during the intrathymic differentiation process.

2022-04-27 | GSE178889 | GEO

IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4+Foxp3+ regulatory T lymphocytes

Project description:Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. In three-week-old mice, when substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 and IL-15 differentially modulated the CD25, GITR, OX40, and CD73-phenotypes of thymus-egress-competent and periphery-seeding Treg. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3sf mice, thymus-exit-competent Treg from IL-2- (and to a lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.

2022-08-29 | GSE153484 | GEO

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