Park2019 - IL7 receptor signaling in T cells
Model Identifier
BIOMD0000000803
Short description
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.
Format
SBML
(L2V4)
Related Publication
-
IL7 receptor signaling in T cells: A mathematical modeling perspective.
- Park JH, Waickman AT, Reynolds J, Castro M, Molina-París C
- Wiley interdisciplinary reviews. Systems biology and medicine , 9/ 2019 , Volume 11 , Issue 5 , pages: e1447 , PubMed ID: 31137085
- Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland.
- 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 c 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 c 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.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Rahuman Sheriff
Modellers: Rahuman Sheriff, Johannes Meyer
Submitter of this revision: Rahuman Sheriff
Modellers: Rahuman Sheriff, Johannes Meyer
Metadata information
is (2 statements)
isDerivedFrom (1 statement)
hasProperty (2 statements)
isDescribedBy (1 statement)
isDerivedFrom (1 statement)
hasProperty (2 statements)
Mathematical Modelling Ontology
Ordinary differential equation model
Gene Ontology T cell homeostasis
Gene Ontology T cell homeostasis
isDescribedBy (1 statement)
Curation status
Curated
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| Park2019.xml | SBML L2V4 Representation of Park2019 - IL7 receptor signaling in T cells | 35.63 KB | Preview | Download |
Additional files |
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| Park2019.cps | COPASI file of Park2019 - IL7 receptor signaling in T cells | 59.87 KB | Preview | Download |
| Park2019.sedml | SED-ML file of Park2019 - IL7 receptor signaling in T cells | 4.22 KB | Preview | Download |
- Model originally submitted by : Johannes Meyer
- Submitted: Aug 21, 2019 11:41:19 AM
- Last Modified: Oct 5, 2021 1:08:28 PM
Revisions
-
Version: 4
- Submitted on: Oct 5, 2021 1:08:28 PM
- Submitted by: Rahuman Sheriff
- With comment: Automatically added model identifier BIOMD0000000803
-
Version: 2
- Submitted on: Aug 21, 2019 11:41:19 AM
- Submitted by: Johannes Meyer
- With comment: Automatically added model identifier BIOMD0000000803
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Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
| Species | Initial Concentration/Amount |
|---|---|
| IL7Ru 159734 |
0.0 nmol |
| IL15Ru Interleukin-15 Receptor |
0.0 nmol |
| IL7Rb interleukin-7 receptor complex |
0.0 nmol |
| IL15Rb interleukin-15 receptor complex |
0.0 nmol |
| IL7Ra Interleukin-7 Receptor Subunit Alpha |
1000.0 nmol |
| gamma c PR:P31785 |
100000.0 nmol |
| IL15 Interleukin-15 |
602.214 nmol |
Reactions
| Reactions | Rate | Parameters |
|---|---|---|
| IL7 + IL7Ru => IL7Rb | compartment*k_f_3*IL7*IL7Ru | k_f_3 = 1.66054E-4 |
| IL15Rb => IL15 + IL15Ru | compartment*k_r_4*IL15Rb | k_r_4 = 0.1 |
| IL7Rb => IL7 + IL7Ru | compartment*k_r_3*IL7Rb | k_r_3 = 0.1 |
| IL15 + IL15Ru => IL15Rb | compartment*k_f_4*IL15*IL15Ru | k_f_4 = 1.66054E-5 |
| IL7Ru => IL7Ra + gamma_c | compartment*k_r_1*IL7Ru | k_r_1 = 0.1 |
| IL7Ra + gamma_c => IL7Ru | compartment*k_f_1*IL7Ra*gamma_c | k_f_1 = 1.66054E-4 |
| IL15Rbeta + gamma_c => IL15Ru | compartment*k_f_2*IL15Rbeta*gamma_c | k_f_2 = 1.66054E-4 |
Curator's comment:
(added: 21 Aug 2019, 11:41:13, updated: 21 Aug 2019, 11:41:13)
(added: 21 Aug 2019, 11:41:13, updated: 21 Aug 2019, 11:41:13)
Reproduced plot of Figure 2, left pane in the original publication. Initial conditions and parameters were modified as indicated by the BioNetGen script given in Appendix A.
Model simulated and plot produced using COPASI 4.24 (Build 197).