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BIOMD0000000451 - Carbo2013 - Cytokine driven CD4+ T Cell differentiation and phenotype plasticity

 

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Reference Publication
Publication ID: 23592971
Carbo A, Hontecillas R, Kronsteiner B, Viladomiu M, Pedragosa M, Lu P, Philipson CW, Hoops S, Marathe M, Eubank S, Bisset K, Wendelsdorf K, Jarrah A, Mei Y, Bassaganya-Riera J.
Systems modeling of molecular mechanisms controlling cytokine-driven CD4+ T cell differentiation and phenotype plasticity.
PLoS Comput. Biol. 2013 Apr; 9(4): e1003027
Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, USA.  [more]
Model
Original Model: BIOMD0000000451.origin
Submitter: Adria Carbo
Submission ID: MODEL1304230001
Submission Date: 23 Apr 2013 20:18:47 UTC
Last Modification Date: 10 Oct 2014 12:12:39 UTC
Creation Date: 09 May 2013 15:36:48 UTC
Encoders:  Vijayalakshmi Chelliah
   Adria Carbo
set #1
bqbiol:hasTaxon Taxonomy Mus musculus
set #2
bqbiol:occursIn Brenda Tissue Ontology gut
set #3
bqbiol:hasProperty Mathematical Modelling Ontology ordinary differential equation model
set #4
bqbiol:isVersionOf Gene Ontology CD4 biosynthetic process
Gene Ontology T cell differentiation
set #5
bqbiol:hasProperty Human Disease Ontology bacterial infectious disease
Notes
Carbo2013 - Cytokine driven CD4+ T Cell differentiation and phenotype plasticity

CD4+ T cells can differentiate into different phenotypes depending on the cytokine milieu. Here a computational and mathematical model with sixty ordinary differential equations representing a CD4+ T cell differentiating into either Th1, Th2, Th17 or iTreg cells, has been constructed. The model includes cytokines, nuclear receptors and transcription factors that define fate and function of CD4+ T cells. Computational simulations illustrate how a proinflammatory Th17 cell can undergo reprogramming into an anti-inflammatory iTreg phenotype following PPARc activation.

This model is described in the article:

Carbo A, Hontecillas R, Kronsteiner B, Viladomiu M, Pedragosa M, Lu P, Philipson CW, Hoops S, Marathe M, Eubank S, Bisset K, Wendelsdorf K, Jarrah A, Mei Y, Bassaganya-Riera J
PLoS Computational Biology [2013, 9(4):e1003027]

Abstract:

Differentiation of CD4+ T cells into effector or regulatory phenotypes is tightly controlled by the cytokine milieu, complex intracellular signaling networks and numerous transcriptional regulators. We combined experimental approaches and computational modeling to investigate the mechanisms controlling differentiation and plasticity of CD4+ T cells in the gut of mice. Our computational model encompasses the major intracellular pathways involved in CD4+ T cell differentiation into T helper 1 (Th1), Th2, Th17 and induced regulatory T cells (iTreg). Our modeling efforts predicted a critical role for peroxisome proliferator-activated receptor gamma (PPARγ) in modulating plasticity between Th17 and iTreg cells. PPARγ regulates differentiation, activation and cytokine production, thereby controlling the induction of effector and regulatory responses, and is a promising therapeutic target for dysregulated immune responses and inflammation. Our modeling efforts predict that following PPARγ activation, Th17 cells undergo phenotype switch and become iTreg cells. This prediction was validated by results of adoptive transfer studies showing an increase of colonic iTreg and a decrease of Th17 cells in the gut mucosa of mice with colitis following pharmacological activation of PPARγ. Deletion of PPARγ in CD4+ T cells impaired mucosal iTreg and enhanced colitogenic Th17 responses in mice with CD4+ T cell-induced colitis. Thus, for the first time we provide novel molecular evidence in vivo demonstrating that PPARγ in addition to regulating CD4+ T cell differentiation also plays a major role controlling Th17 and iTreg plasticity in the gut mucosa.

Author's comment: CD4+ T cell computational model (Version 1.4) Steady state corrected. There was a problem in the internalization of IL-17 in its mathematical function.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 23592971 Submission Date: 23 Apr 2013 20:18:47 UTC Last Modification Date: 10 Oct 2014 12:12:39 UTC Creation Date: 09 May 2013 15:36:48 UTC
Mathematical expressions
Reactions
re2 re3 re6 re8
re9 re10 re11 re12
re13 re14 re15 re16
re17 re18 re19 re20
re23 re24 re25 re26
re27 re28 re29 re30
re31 re32 re33 re34
re35 re36 re37 re38
re42 re44 re45 re46
re48 re49 re50 re47
re51 IL18 pool IL12 pool IFNg pool
IL21 pool IL23 pool IL17 pool IL10 pool
IL6 pool IL2 pool TGFb pool IL4 pool
re52      
Rules
Assignment Rule (variable: FOXP3R) Assignment Rule (variable: IL17R)    
Physical entities
Compartments Species
default eIFNg eIL12 eIL21
eIL23 eIL4 eTGFb
eIL2 eIL6 eIL17
eIL10 eIL18 anti-IL4
anti-IFNg pIL4 IL18_pool
IL12_pool IFNg_pool IL21_pool
IL23_pool IL17_pool IL10_pool
IL6_pool IL2_pool TGFb_pool
IL4_pool pIL10  
T Helper Cell IL6-IL6R IL6R IL6
TGFb-TGFbR TGFbR TGFb
IL2-IL2R IL2R IL2
IL4-IL4R IL4R IL4
IFNg-IFNgR IFNgR IL12-IL12R
IL12R IL12 IL18-IL18R
IL18R IL18 IL21
IL21-IL21R IL21R IL23R
IL23-IL23R IL10R IL10-IL10R
IRAK1 IRAK1-P p50/p65 dimer
STAT4 STAT4-P IFNg
JAK1 JAK1-P STAT1
STAT1-P p40/p19 dimer IL17
IL10 RORgt RORgt-ligand
STAT3-P STAT3 STAT5-P
STAT5 FOXP3 SOCS1
SOCS1-JAKs Tbet-P Tbet
GATA3 GATA3-P STAT6-P
STAT6 PPARg L-PPARg
Ligand acetylated FOXP3 p19
p40 p50 p65
IL17R IL17-IL17R pIFNg
pIL21 pIL17  
Global parameters
Hill Coeficient BActin FOXP3R IL17R
Initial for BActin      
Reactions (53)
 
 re2 [eIL18] + [IL18R] ↔ [IL18-IL18R];   {STAT6-P} , {eIL18} , {IL18R} , {STAT6-P} , {IL18-IL18R}
 
 re3 [IRAK1] ↔ [IRAK1-P];   {IL18-IL18R} , {IRAK1} , {IL18-IL18R} , {IRAK1-P}
 
 re6 [IL12] → [eIL12];   {IL12}
 
 re8 [eIL12] + [IL12R] ↔ [IL12-IL12R];   {STAT6-P} , {L-PPARg} , {eIL12} , {IL12R} , {STAT6-P} , {L-PPARg} , {IL12-IL12R}
 
 re9 [p50] + [p65] ↔ [p50/p65 dimer];   {L-PPARg} , {acetylated FOXP3} , {IRAK1-P} , {L-PPARg} , {acetylated FOXP3} , {IRAK1-P} , {p50/p65 dimer} , {p50} , {p65}
 
 re10 [STAT4] ↔ [STAT4-P];   {IL21-IL21R} , {GATA3-P} , {IL12-IL12R} , {IL23-IL23R} , {STAT4} , {IL21-IL21R} , {GATA3-P} , {IL12-IL12R} , {IL23-IL23R} , {STAT4-P}
 
 re11 [eIFNg] + [IFNgR] ↔ [IFNg-IFNgR];   {SOCS1-JAKs} , {eIFNg} , {IFNgR} , {SOCS1-JAKs} , {IFNg-IFNgR}
 
 re12 [IFNg] → [eIFNg];   {IFNg}
 
 re13 [STAT1] ↔ [STAT1-P];   {L-PPARg} , {IL21-IL21R} , {IFNg-IFNgR} , {JAK1-P} , {STAT1} , {L-PPARg} , {IL21-IL21R} , {IFNg-IFNgR} , {JAK1-P} , {STAT1-P}
 
 re14 [pIFNg] ↔ [IFNg];   {anti-IFNg} , {STAT3-P} , {L-PPARg} , {STAT4-P} , {p50/p65 dimer} , {Tbet-P} , {pIFNg} , {anti-IFNg} , {STAT3-P} , {L-PPARg} , {STAT4-P} , {p50/p65 dimer} , {Tbet-P} , {IFNg}
 
 re15 [Tbet] ↔ [Tbet-P];   {TGFb-TGFbR} , {STAT3-P} , {STAT4-P} , {STAT1-P} , {Tbet-P} , {Tbet} , {TGFb-TGFbR} , {STAT3-P} , {STAT4-P} , {STAT1-P} , {Tbet-P}
 
 re16 [JAK1] ↔ [JAK1-P];   {L-PPARg} , {SOCS1-JAKs} , {IFNg-IFNgR} , {JAK1} , {L-PPARg} , {SOCS1-JAKs} , {IFNg-IFNgR} , {JAK1-P}
 
 re17 [SOCS1] ↔ [SOCS1-JAKs];   {STAT1-P} , {Tbet-P} , {SOCS1} , {STAT1-P} , {Tbet-P} , {SOCS1-JAKs}
 
 re18 [IL4] → [eIL4];   {IL4}
 
 re19 [eIL4] + [IL4R] ↔ [IL4-IL4R];   {SOCS1-JAKs} , {eIL4} , {IL4R} , {SOCS1-JAKs} , {IL4-IL4R}
 
 re20 [pIL4] ↔ [IL4];   {STAT1-P} , {anti-IL4} , {IL4} , {GATA3-P} , {STAT5-P} , {pIL4} , {STAT1-P} , {anti-IL4} , {IL4} , {GATA3-P} , {STAT5-P}
 
 re23 [GATA3] ↔ [GATA3-P];   {Tbet-P} , {STAT3-P} , {TGFb-TGFbR} , {STAT6-P} , {L-PPARg} , {GATA3} , {Tbet-P} , {STAT3-P} , {TGFb-TGFbR} , {STAT6-P} , {L-PPARg} , {GATA3-P}
 
 re24 [STAT6] ↔ [STAT6-P];   {IFNg-IFNgR} , {IL4-IL4R} , {STAT6} , {IFNg-IFNgR} , {IL4-IL4R} , {STAT6-P}
 
 re25 [eIL2] + [IL2R] ↔ [IL2-IL2R];   {eIL2} , {IL2R} , {IL2-IL2R}
 
 re26 [STAT5] ↔ [STAT5-P];   {IL2-IL2R} , {STAT5} , {IL2-IL2R} , {STAT5-P}
 
 re27 [FOXP3] ↔ [acetylated FOXP3];   {STAT6-P} , {STAT3-P} , {IL6-IL6R} , {TGFb-TGFbR} , {STAT1-P} , {STAT5-P} , {L-PPARg} , {FOXP3} , {STAT6-P} , {STAT3-P} , {IL6-IL6R} , {TGFb-TGFbR} , {STAT1-P} , {STAT5-P} , {L-PPARg} , {acetylated FOXP3}
 
 re28 [eTGFb] + [TGFbR] ↔ [TGFb-TGFbR];   {eTGFb} , {TGFbR} , {TGFb-TGFbR}
 
 re29 [eIL6] + [IL6R] ↔ [IL6-IL6R];   {eIL6} , {IL6R} , {IL6-IL6R}
 
 re30 [STAT3] ↔ [STAT3-P];   {L-PPARg} , {IL21-IL21R} , {IL23-IL23R} , {IL10-IL10R} , {IL6-IL6R} , {STAT3} , {L-PPARg} , {IL21-IL21R} , {IL23-IL23R} , {IL10-IL10R} , {IL6-IL6R} , {STAT3-P}
 
 re31 [RORgt] ↔ [RORgt-ligand];   {acetylated FOXP3} , {L-PPARg} , {STAT3-P} , {TGFb-TGFbR} , {RORgt} , {acetylated FOXP3} , {L-PPARg} , {STAT3-P} , {TGFb-TGFbR} , {RORgt-ligand}
 
 re32 [eIL21] + [IL21R] ↔ [IL21-IL21R];   {STAT5-P} , {IL17-IL17R} , {eIL21} , {IL21R} , {STAT5-P} , {IL17-IL17R} , {IL21-IL21R}
 
 re33 [IL21] → [eIL21];   {IL21}
 
 re34 [eIL23] ↔ [p40/p19 dimer];   {eIL23} , {p40/p19 dimer}
 
 re35 [p40/p19 dimer] + [IL23R] ↔ [IL23-IL23R];   {Tbet-P} , {p40/p19 dimer} , {IL23R} , {Tbet-P} , {IL23-IL23R}
 
 re36 [p40] + [p19] ↔ [p40/p19 dimer];   {L-PPARg} , {IL6-IL6R} , {p40} , {p19} , {L-PPARg} , {IL6-IL6R} , {p40/p19 dimer}
 
 re37 [pIL21] ↔ [IL21];   {STAT3-P} , {pIL21} , {STAT3-P} , {IL21}
 
 re38 [eIL10] + [IL10R] ↔ [IL10-IL10R];   {eIL10} , {IL10R} , {IL10-IL10R}
 
 re42 [PPARg] + [Ligand] ↔ [L-PPARg];   {IFNg-IFNgR} , {IL4-IL4R} , {PPARg} , {Ligand} , {IFNg-IFNgR} , {IL4-IL4R} , {L-PPARg}
 
 re44 [TGFb] → [eTGFb];   {TGFb}
 
 re45 [IL2] → [eIL2];   {IL2}
 
 re46 [IL6] → [eIL6];   {IL6}
 
 re48 [IL10] → [eIL10];   {IL10}
 
 re49 [IL17] → [eIL17];   {IL17}
 
 re50 [eIL17] + [IL17R] ↔ [IL17-IL17R];   {eIL17} , {IL17R} , {IL17-IL17R}
 
 re47 [IL18] → [eIL18];   {IL18}
 
 re51 [pIL17] ↔ [IL17];   {L-PPARg} , {IL23-IL23R} , {RORgt-ligand} , {STAT4-P} , {pIL17} , {L-PPARg} , {IL23-IL23R} , {RORgt-ligand} , {STAT4-P} , {IL17}
 
 IL18 pool [IL18_pool] ↔ [eIL18];   {IL18_pool} , {eIL18}
 
 IL12 pool [IL12_pool] ↔ [eIL12];   {IL12_pool} , {eIL12}
 
 IFNg pool [IFNg_pool] ↔ [eIFNg];   {IFNg_pool} , {eIFNg}
 
 IL21 pool [IL21_pool] ↔ [eIL21];   {IL21_pool} , {eIL21}
 
 IL23 pool [IL23_pool] ↔ [eIL23];   {IL23_pool} , {eIL23}
 
 IL17 pool [IL17_pool] ↔ [IL17];   {IL17_pool} , {IL17}
 
 IL10 pool [IL10_pool] ↔ [eIL10];   {IL10_pool} , {eIL10}
 
 IL6 pool [IL6_pool] ↔ [eIL6];   {IL6_pool} , {eIL6}
 
 IL2 pool [IL2_pool] ↔ [eIL2];   {IL2_pool} , {eIL2}
 
 TGFb pool [TGFb_pool] ↔ [eTGFb];   {TGFb_pool} , {eTGFb}
 
 IL4 pool [IL4_pool] ↔ [eIL4];   {IL4_pool} , {eIL4}
 
 re52 [pIL10] ↔ [IL10];   {IL23-IL23R} , {L-PPARg} , {IL21-IL21R} , {GATA3-P} , {STAT5-P} , {pIL10} , {IL23-IL23R} , {L-PPARg} , {IL21-IL21R} , {GATA3-P} , {STAT5-P} , {IL10}
 
Rules (2)
 
 Assignment Rule (name: parameter_3) FOXP3R = s40/ModelValue_5
 
 Assignment Rule (name: parameter_4) IL17R = s73/ModelValue_5
 
Functions (16)
 
 2 Reactants, 1 Inhibitor lambda(Vf, r1, r2, K, n, I, Vr, p, Vf*r1*r2*K^n/(I^n+K^n)-Vr*p)
 
 1 Reactant, 1 Activator lambda(Vf, r1, A, n, K, Vr, p, Vf*r1*(1+A^n/(A^n+K^n))-Vr*p)
 
 2 Reactants, 2 Inhibitors lambda(Vf, r1, r2, K1, n1, I1, K2, n2, I2, Vr, p, Vf*r1*r2*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)-Vr*p)
 
 2 Reactants, 2 Inhibitors, 1 Activator lambda(Vf, K1, n1, I1, K2, n2, I2, A, n3, K3, Vr, p, r1, r2, Vf*r1*r2*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)*(1+A^n3/(A^n3+K3^n3))-Vr*p)
 
 1 Reactant, 1 Inhibitor, 3 Activators lambda(Vf, r1, K, n, I, A1, n1, K1, A2, n2, K2, A3, n3, K3, Vr, p, Vf*r1*K^n/(I^n+K^n)*(A1^n1/(A1^n1+K1^n1)+A2^n2/(A2^n2+K2^n2)+A3^n3/(A3^n3+K3^n3))-Vr*p)
 
 1 Reactant, 3 Inhibitors, 3 Activators lambda(Vf, r1, K1, n1, I1, K2, n2, I2, K3, n3, I3, A1, n4, K4, A2, n5, K5, A3, n6, K6, Vr, p, Vf*r1*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)*K3^n3/(I3^n3+K3^n3)*(A1^n4/(A1^n4+K4^n4)+A2^n5/(A2^n5+K5^n5)+A3^n6/(A3^n6+K6^n6))-Vr*p)
 
 1 Reactant, 2 Inhibitors, 1 Activator lambda(Vf, r1, K1, n1, I1, K2, n2, I2, A, n3, K3, Vr, p, Vf*r1*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)*(1+A^n3/(A^n3+K3^n3))-Vr*p)
 
 1 Reactant, 2 Activators lambda(Vf, r1, A1, n1, K1, A2, n2, K2, Vr, p, Vf*r1*A1^n1/(A1^n1+K1^n1)*A2^n2/(A2^n2+K2^n2)-Vr*p)
 
 1 Reactant, 3 Inhibitors, 2 Activators lambda(Vf, r1, K1, n1, I1, K2, n2, I2, K3, n3, I3, A1, n4, K4, A2, n5, K5, Vr, p, Vf*r1*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)*K3^n3/(I3^n3+K3^n3)*(A1^n4/(A1^n4+K4^n4)+A2^n5/(A2^n5+K5^n5))-Vr*p)
 
 1 Reactant, 1 Inhibitor, 4 Activators lambda(Vf, r1, K, n, I, A1, n1, K1, A2, n2, K2, A3, n3, K3, A4, n4, K4, Vr, p, Vf*r1*K^n/(I^n+K^n)*(A1^n1/(A1^n1+K1^n1)+A2^n2/(A2^n2+K2^n2)+A3^n3/(A3^n3+K3^n3)+A4^n4/(A4^n4+K4^n4))-Vr*p)
 
 2 Reactants, 1 Inhibitor, 1 Activator lambda(Vf, r1, r2, K, n, I, A, n1, K1, Vr, p, Vf*r1*r2*K^n/(I^n+K^n)*(1+A^n1/(A^n1+K1^n1))-Vr*p)
 
 1 Reactant, 3 Inhibitors, 4 Activators lambda(Vf, r1, K1, n1, I1, K2, n2, I2, K3, n3, I3, A1, n4, K4, A2, n5, K5, A3, n6, K6, A4, n7, K7, Vr, p, Vf*r1*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)*K3^n3/(I3^n3+K3^n3)*(A1^n4/(A1^n4+K4^n4)+A2^n5/(A2^n5+K5^n5)+A3^n6/(A3^n6+K6^n6)+A4^n7/(A4^n7+K7^n7))-Vr*p)
 
 1 Reactant, 2 Inhibitors, 2 Activators lambda(Vf, r1, K1, n1, I1, K2, n2, I2, A1, n3, K3, A2, n4, K4, Vr, p, Vf*r1*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)*(A1^n3/(A1^n3+K3^n3)+A2^n4/(A2^n4+K4^n4))-Vr*p)
 
 1 Reactant, 2 Inhibitors, 3 Activators lambda(Vf, r1, K1, n1, I1, K2, n2, I2, A1, n3, K3, A2, n4, K4, A3, n5, K5, Vr, p, Vf*r1*K1^n1/(I1^n1+K1^n1)*K2^n2/(I2^n2+K2^n2)*(A1^n3/(A1^n3+K3^n3)+A2^n4/(A2^n4+K4^n4)+A3^n5/(A3^n5+K5^n5))-Vr*p)
 
 1 Reactant, 1 inhibitor, 1 activator lambda(Vf, r1, K, n, I, A1, n1, K1, Vr, p, Vf*r1*K^n/(I^n+K^n)*A1^n1/(A1^n1+K1^n1)-Vr*p)
 
 Pool coupling lambda(V, pool, n, ext, k, V*(pool^n/(pool^n+ext^n+0.001)-k*ext))
 
 default Spatial dimensions: 3.0  Compartment size: 1.0
 
 eIFNg
Compartment: default
Initial concentration: 0.0
 
 eIL12
Compartment: default
Initial concentration: 0.0
 
 eIL21
Compartment: default
Initial concentration: 0.0
 
 eIL23
Compartment: default
Initial concentration: 0.0
 
 eIL4
Compartment: default
Initial concentration: 0.0
 
 eTGFb
Compartment: default
Initial concentration: 1.0
 
 eIL2
Compartment: default
Initial concentration: 0.0
 
 eIL6
Compartment: default
Initial concentration: 1.0
 
 eIL17
Compartment: default
Initial concentration: 0.0
 
 eIL10
Compartment: default
Initial concentration: 0.0
 
 eIL18
Compartment: default
Initial concentration: 0.0
 
 anti-IL4
Compartment: default
Initial concentration: 1.0
Constant
 
 anti-IFNg
Compartment: default
Initial concentration: 1.0
Constant
 
 pIL4
Compartment: default
Initial concentration: 1.0
Constant
 
 IL18_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 IL12_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 IFNg_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 IL21_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 IL23_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 IL17_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 IL10_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 IL6_pool
Compartment: default
Initial concentration: 1.0
Constant
 
 IL2_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 TGFb_pool
Compartment: default
Initial concentration: 1.0
Constant
 
 IL4_pool
Compartment: default
Initial concentration: 0.0
Constant
 
 pIL10
Compartment: default
Initial concentration: 1.0
Constant
 
 T Helper Cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 IL6-IL6R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL6R
Compartment: T Helper Cell
Initial concentration: 0.9999999518
 
 IL6
Compartment: T Helper Cell
Initial concentration: 0.0
 
 TGFb-TGFbR
Compartment: T Helper Cell
Initial concentration: 0.0
 
 TGFbR
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 TGFb
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL2-IL2R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL2R
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL2
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL4-IL4R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL4R
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL4
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IFNg-IFNgR
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IFNgR
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL12-IL12R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL12R
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL12
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL18-IL18R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL18R
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL18
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL21
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL21-IL21R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL21R
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL23R
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL23-IL23R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL10R
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
 
 IL10-IL10R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IRAK1
Compartment: T Helper Cell
Initial concentration: 0.5
Constant
 
 IRAK1-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 p50/p65 dimer
Compartment: T Helper Cell
Initial concentration: 0.0
 
 STAT4
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 STAT4-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IFNg
Compartment: T Helper Cell
Initial concentration: 0.0
 
 JAK1
Compartment: T Helper Cell
Initial concentration: 0.5
Constant
 
 JAK1-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 STAT1
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 STAT1-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 p40/p19 dimer
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL17
Compartment: T Helper Cell
Initial concentration: 0.0
 
 IL10
Compartment: T Helper Cell
Initial concentration: 0.0
 
 RORgt
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 RORgt-ligand
Compartment: T Helper Cell
Initial concentration: 0.0
 
 STAT3-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 STAT3
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 STAT5-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 STAT5
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 FOXP3
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 SOCS1
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 SOCS1-JAKs
Compartment: T Helper Cell
Initial concentration: 0.0
 
 Tbet-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 Tbet
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 GATA3
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 GATA3-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 STAT6-P
Compartment: T Helper Cell
Initial concentration: 0.0
 
 STAT6
Compartment: T Helper Cell
Initial concentration: 1.0
Constant
 
 PPARg
Compartment: T Helper Cell
Initial concentration: 0.08
 
 L-PPARg
Compartment: T Helper Cell
Initial concentration: 0.0
 
 Ligand
Compartment: T Helper Cell
Initial concentration: 0.9999999518
Constant
 
 acetylated FOXP3
Compartment: T Helper Cell
Initial concentration: 0.0
 
 p19
Compartment: T Helper Cell
Initial concentration: 0.9999999518
Constant
 
 p40
Compartment: T Helper Cell
Initial concentration: 0.9999999518
Constant
 
 p50
Compartment: T Helper Cell
Initial concentration: 0.5
Constant
 
 p65
Compartment: T Helper Cell
Initial concentration: 0.5
Constant
 
 IL17R
Compartment: T Helper Cell
Initial concentration: 0.9999999518
 
 IL17-IL17R
Compartment: T Helper Cell
Initial concentration: 0.0
 
 pIFNg
Compartment: T Helper Cell
Initial concentration: 0.9999999518
Constant
 
 pIL21
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
 pIL17
Compartment: T Helper Cell
Initial concentration: 0.999999951844375
Constant
 
Global Parameters (5)
 
 Hill Coeficient
Value: 2.0
Constant
 
 BActin
Value: 0.00850607781012331
Constant
 
  FOXP3R  
 
  IL17R  
 
 Initial for BActin
Value: 0.00850607781012331
Constant
 
re2 (3)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.138094
Constant
 
   Vr
Value: 0.1
Constant
 
re3 (3)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 2.01676
Constant
 
   Vr
Value: 0.1
Constant
 
re6 (1)
 
   k1
Value: 0.1
Constant
 
re8 (4)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 2.94611
Constant
 
   K2
Value: 0.743847
Constant
 
   Vr
Value: 0.1
Constant
 
re9 (5)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 0.1
Constant
 
   K2
Value: 98.9482
Constant
 
   K3
Value: 0.0539426
Constant
 
   Vr
Value: 0.1
Constant
 
re10 (6)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 0.125481
Constant
 
   K2
Value: 0.896854
Constant
 
   K3
Value: 0.031433
Constant
 
   K4
Value: 66.6168
Constant
 
   Vr
Value: 0.1
Constant
 
re11 (3)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.263953
Constant
 
   Vr
Value: 0.1
Constant
 
re12 (1)
 
   k1
Value: 0.1
Constant
 
re13 (6)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.1
Constant
 
   K1
Value: 5.04432
Constant
 
   K2
Value: 0.0705365
Constant
 
   K3
Value: 14.9778
Constant
 
   Vr
Value: 0.1
Constant
 
re14 (8)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 0.501917
Constant
 
   K2
Value: 0.812366
Constant
 
   K3
Value: 0.1
Constant
 
   K4
Value: 0.001477
Constant
 
   K5
Value: 100.0
Constant
 
   K6
Value: 0.230841
Constant
 
   Vr
Value: 0.1
Constant
 
re15 (7)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 0.916783
Constant
 
   K2
Value: 1.33537
Constant
 
   K3
Value: 3.58849
Constant
 
   K4
Value: 0.727962
Constant
 
   K5
Value: 6.97805
Constant
 
   Vr
Value: 0.1
Constant
 
re16 (5)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 0.1
Constant
 
   K2
Value: 0.004433
Constant
 
   K3
Value: 99.987
Constant
 
   Vr
Value: 0.1
Constant
 
re17 (4)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 7.83763
Constant
 
   K2
Value: 0.667462
Constant
 
   Vr
Value: 0.1
Constant
 
re18 (1)
 
   k1
Value: 0.1
Constant
 
re19 (3)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 13.0657
Constant
 
   Vr
Value: 0.1
Constant
 
re20 (7)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 0.210399
Constant
 
   K2
Value: 56.3452
Constant
 
   K3
Value: 98.0373
Constant
 
   K4
Value: 0.855534
Constant
 
   K5
Value: 4.32731
Constant
 
   Vr
Value: 0.1
Constant
 
re23 (7)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 0.199351
Constant
 
   K2
Value: 9.61521
Constant
 
   K3
Value: 0.214012
Constant
 
   K4
Value: 0.321065
Constant
 
   K5
Value: 0.1
Constant
 
   Vr
Value: 0.1
Constant
 
re24 (5)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.1
Constant
 
   n1
Value: 0.004304
Constant
 
   K1
Value: 0.1
Constant
 
   Vr
Value: 0.1
Constant
 
re25 (2)
 
   k1
Value: 0.1
Constant
 
   k2
Value: 0.1
Constant
 
re26 (3)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.374591
Constant
 
   Vr
Value: 0.1
Constant
 
re27 (9)
 
   Vf
Value: 0.1
Constant
 
   K1
Value: 100.0
Constant
 
   K2
Value: 0.354892
Constant
 
   K3
Value: 1.31281
Constant
 
   K4
Value: 6.79025E-4
Constant
 
   K5
Value: 2.07945
Constant
 
   K6
Value: 100.0
Constant
 
   K7
Value: 1.93254E-7
Constant
 
   Vr
Value: 0.1
Constant
 
re28 (2)
 
   k1
Value: 0.1
Constant
 
   k2
Value: 0.1
Constant
 
re29 (2)
 
   k1
Value: 0.1
Constant
 
   k2
Value: 0.1
Constant
 
re30 (7)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.1
Constant
 
   K1
Value: 0.636796
Constant
 
   K2
Value: 39.018
Constant
 
   K3
Value: 2.26986
Constant
 
   K4
Value: 0.137545
Constant
 
   Vr
Value: 0.1
Constant
 
re31 (6)
 
   Vf
Value: 0.2249
Constant
 
   K1
Value: 9722.09
Constant
 
   K2
Value: 0.703778
Constant
 
   K3
Value: 1.24123
Constant
 
   K4
Value: 997.263
Constant
 
   Vr
Value: 0.1
Constant
 
re32 (4)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.240705
Constant
 
   K1
Value: 8.14189
Constant
 
   Vr
Value: 0.1
Constant
 
re33 (1)
 
   k1
Value: 0.1
Constant
 
re34 (2)
 
   k1
Value: 0.1
Constant
 
   k2
Value: 0.1
Constant
 
re35 (3)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 4.66107
Constant
 
   Vr
Value: 0.1
Constant
 
re36 (4)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.1
Constant
 
   K1
Value: 25.5354
Constant
 
   Vr
Value: 0.1
Constant
 
re37 (3)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.118892
Constant
 
   Vr
Value: 0.1
Constant
 
re38 (2)
 
   k1
Value: 0.1
Constant
 
   k2
Value: 0.1
Constant
 
re42 (4)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.1
Constant
 
   K1
Value: 0.1
Constant
 
   Vr
Value: 0.1
Constant
 
re44 (1)
 
   k1
Value: 0.1
Constant
 
re45 (1)
 
   k1
Value: 0.1
Constant
 
re46 (1)
 
   k1
Value: 0.1
Constant
 
re48 (1)
 
   k1
Value: 0.1
Constant
 
re49 (1)
 
   k1
Value: 0.1
Constant
 
re50 (2)
 
   k1
Value: 0.184881
Constant
 
   k2
Value: 0.1896
Constant
 
re47 (1)
 
   k1
Value: 0.1
Constant
 
re51 (6)
 
   Vf
Value: 0.225095
Constant
 
   K
Value: 0.1
Constant
 
   K1
Value: 1.62893
Constant
 
   K2
Value: 0.526832
Constant
 
   K3
Value: 5.47889
Constant
 
   Vr
Value: 0.1
Constant
 
IL18 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.5
Constant
 
IL12 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.5
Constant
 
IFNg pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
IL21 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
IL23 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
IL17 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
IL10 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
IL6 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
IL2 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
TGFb pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
IL4 pool (2)
 
   V
Value: 0.1
Constant
 
   k
Value: 0.1
Constant
 
re52 (7)
 
   Vf
Value: 0.1
Constant
 
   K
Value: 0.508159
Constant
 
   K1
Value: 0.1
Constant
 
   K2
Value: 0.00125893
Constant
 
   K3
Value: 0.645162
Constant
 
   K4
Value: 100.0
Constant
 
   Vr
Value: 0.1
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000451

Curator's comment: (updated: 09 May 2013 15:36:34 GMT)

Figure 3a (Th17 Wild-type) has been reproduced here. The model was simulated using SBML odeSolver. The plots were obtained using Gnuplot.

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