{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=curation_notes.txt"],"Owl":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=Park2019-biopax3.owl","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=Park2019-biopax2.owl"],"Xml":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=Park2019.xml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=manifest.xml"],"Other":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=Park2019.sedml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=curation_image.png","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=metadata.rdf","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000803?filename=Park2019.cps"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["Johannes Meyer"],"curationStatus":["Manually curated"],"modellingApproach":["ordinary differential equation model"],"levelVersion":["L2V4"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/BIOMD0000000803"],"publication_pubmed":["31137085"],"isPrivate":["false"],"repository":["BioModels"],"modelFormat":["SBML"],"omics_type":["Models"],"tokenised_name":["Park2019   IL7 receptor signaling in T cells"],"publication_year":["2019"],"submissionId":["MODEL1908210001"],"publication_authors":["Jung-Hyun Park, Adam T Waickman, Joseph Reynolds, Mario Castro, Carmen Molina-París"],"first_author":["Jung-Hyun Park"],"publication":["31137085,\n                            Interleukin-7 (IL7) plays a nonredundant role in T cell survival and homeostasis, which is illustrated in the severe T cell lymphopenia of IL7-deficient mice, or demonstrated in animals or humans that lack expression of either the IL7Rα or γ <sub>c</sub> chain, the two subunits that constitute the functional IL7 receptor. Remarkably, IL7 is not expressed by T cells themselves, but produced in limited amounts by radio-resistant stromal cells. Thus, T cells need to constantly compete for IL7 to survive. How T cells maintain homeostasis and further maximize the size of the peripheral T cell pool in face of such competition are important questions that have fascinated both immunologists and mathematicians for a long time. Exceptionally, IL7 downregulates expression of its own receptor, so that IL7-signaled T cells do not consume extracellular IL7, and thus, the remaining extracellular IL7 can be shared among unsignaled T cells. Such an altruistic behavior of the IL7Rα chain is quite unique among members of the γ <sub>c</sub> cytokine receptor family. However, the consequences of this altruistic signaling behavior at the molecular, single cell and population levels are less well understood and require further investigation. In this regard, mathematical modeling of how a limited resource can be shared, while maintaining the clonal diversity of the T cell pool, can help decipher the molecular or cellular mechanisms that regulate T cell homeostasis. Thus, the current review aims to provide a mathematical modeling perspective of IL7-dependent T cell homeostasis at the molecular, cellular and population levels, in the context of recent advances in our understanding of the IL7 biology. This article is categorized under: Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Computational Methods.. 5, 11.\n                            Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland."],"submitter_mail":["johannes.p.meyer@gmail.com"],"submitter_affiliation":["EMBL-EBI"],"publicationId":["BIOMD0000000803"],"pubmed_abstract":["Interleukin-7 (IL7) plays a nonredundant role in T cell survival and homeostasis, which is illustrated in the severe T cell lymphopenia of IL7-deficient mice, or demonstrated in animals or humans that lack expression of either the IL7Rα or γ <sub>c</sub> chain, the two subunits that constitute the functional IL7 receptor. Remarkably, IL7 is not expressed by T cells themselves, but produced in limited amounts by radio-resistant stromal cells. Thus, T cells need to constantly compete for IL7 to survive. How T cells maintain homeostasis and further maximize the size of the peripheral T cell pool in face of such competition are important questions that have fascinated both immunologists and mathematicians for a long time. Exceptionally, IL7 downregulates expression of its own receptor, so that IL7-signaled T cells do not consume extracellular IL7, and thus, the remaining extracellular IL7 can be shared among unsignaled T cells. Such an altruistic behavior of the IL7Rα chain is quite unique among members of the γ <sub>c</sub> cytokine receptor family. However, the consequences of this altruistic signaling behavior at the molecular, single cell and population levels are less well understood and require further investigation. In this regard, mathematical modeling of how a limited resource can be shared, while maintaining the clonal diversity of the T cell pool, can help decipher the molecular or cellular mechanisms that regulate T cell homeostasis. Thus, the current review aims to provide a mathematical modeling perspective of IL7-dependent T cell homeostasis at the molecular, cellular and population levels, in the context of recent advances in our understanding of the IL7 biology. This article is categorized under: Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Computational Methods.","Interleukin-7 (IL-7) is an essential cytokine for the development and homeostatic maintenance of T and B lymphocytes. Binding of IL-7 to its cognate receptor, the IL-7 receptor (IL-7R), activates multiple pathways that regulate lymphocyte survival, glucose uptake, proliferation and differentiation. There has been much interest in understanding how IL-7 receptor signaling is modulated at multiple interconnected network levels. This review examines how the strength of the signal through the IL-7 receptor is modulated in T and B cells, including the use of shared receptor components, signaling crosstalk, shared interaction domains, feedback loops, integrated gene regulation, multimerization and ligand competition. We discuss how these network control mechanisms could integrate to govern the properties of IL-7R signaling in lymphocytes in health and disease. Analysis of IL-7 receptor signaling at a network level in a systematic manner will allow for a comprehensive approach to understanding the impact of multiple signaling pathways on lymphocyte biology."],"pubmed_title":["IL7 receptor signaling in T cells: A mathematical modeling perspective.","Interleukin-7 receptor signaling network: an integrated systems perspective."],"pubmed_authors":["Park Jung-Hyun JH, Waickman Adam T AT, Reynolds Joseph J, Castro Mario M, Molina-París Carmen C","Palmer Megan J MJ, Mahajan Vinay S VS, Trajman Lily C LC, Irvine Darrell J DJ, Lauffenburger Douglas A DA, Chen Jianzhu J"],"additional_accession":[]},"is_claimable":false,"name":"Park2019 - IL7 receptor signaling in T cells","description":"\n      \n        This model is an attempt to provide a mathematical description of IL-7 dependent T cell homeostasis at the molecular and cellular level, with inclusion of gamma-chain and ligand binding in the context of receptors for IL-7 and IL-15 receptors.\n      \n    ","dates":{"last_modification":"2024-08-22","publication":"2024-09-02","submission":"2019-08-21"},"accession":"BIOMD0000000803","cross_references":{"sbo":["SBO:0000180"],"pr":["PR:P31785"],"pubmed":["31137085","18445337"],"ncit":["C26278","C26267","C128303","C20510","C20517"],"biomodels__db":["BIOMD0000000803","MODEL1908210001"],"go":["GO:0043029","GO:1905540","GO:1905543","GO:0032403","GO:0005139","GO:0016170"],"orphanet":["159734"],"cl":["CL:0000084"],"doi":["10.1002/wsbm.1447"]}}