1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/17888644.csml convertedTime:2009.07.01.11:07

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Toll-like receptors: paving the path to T cell-driven autoimmunity?
Authors Marsland BJ, Kopf M.
Affiliation Molecular Biomedicine, Institute of Integrative Biology, ETH Zurich, Wagistr 27,8952, Zurich, Switzerland.
Abstract The development of autoimmunity is often associated with the presence ofpathogen-associated molecular patterns (PAMPs) and signaling through toll-likereceptors (TLRs). Largely, the importance of PAMP-TLR ligation has beenattributed to inducing the maturation of antigen-presenting cells and productionof proinflammatory cytokines and chemokines. Recent evidence now shows thatPAMPs can activate effector and regulatory T cells revealing a further level ofcomplexity in the development of autoimmunity. TLR signaling on T cells acts asa form of costimulation, lowering the 'strength of signal' required forproliferation and survival. This apparent mechanism of immune homeostasis maybreak tolerance or anergy upon pathogen infection and promote the development ofimmune responses against self-antigens.
PMID 17888644
Model Abstract

Entity

G011341:IL17 MO000007327:IL-17 MO000007384:IL-6 MO000016808:TGFbeta MO000017777:TCR MO000018458:IL-6R MO000019395:TLRs e1: e10: e11:poly I:C e12:CpG DNA: TLR e13:poly I: C: TLR e14:TCR liagnd: TCR e15:TGFbeta-receptor e16:e16 e17:e17 e2: e3: e4: e5:CpG DNA e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:TCR ligand e60: e61: e62: e7: e8: e9:

Process

p1 p2 p3 p4 p5 p6 p7 p8
Model Detail
550.0, 644.0
40.0, 40.0

IL17

--

G011341

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p8

true true true true

csml-variable:Double

m94226

10

false

infinite

0

unit false false false
TRANSFACG011341

--

Go back
546.0, 484.0
40.0, 40.0

IL-17

--

MO000007327

cso30:c:Protein

cso30:i:CC_CellComponent

--

p8

--

true true true true

csml-variable:Double

m840

10

false

infinite

0

unit false false false
TRANSPATHMO000007327

--

Go back
61.0, 615.0
41.5, 41.5

IL-6

--

MO000007384

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m871

10

false

infinite

0

unit false false false
InterProIPR003573
TRANSPATHMO000007384

--

Go back
66.0, 496.0
32.0, 32.0

TGFbeta

--

MO000016808

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m1746

10

false

infinite

0

unit false false false
TRANSPATHMO000016808

--

Go back
528.0, 150.0
44.0, 44.0

TCR

--

MO000017777

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m2534

10

false

infinite

0

unit false false false
TRANSPATHMO000017777

--

Go back
143.0, 621.0
38.0, 38.0

IL-6R

--

MO000018458

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m3096

10

false

infinite

0

unit false false false
InterProIPR003961
TRANSPATHMO000018458

--

Go back
286.0, 152.0
34.0, 34.0

TLRs

--

MO000019395

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p2

true true true true

csml-variable:Double

m3962

10

false

infinite

0

unit false false false
TRANSPATHMO000019395

--

Go back
130.75, 139.9969080091176
856.2594311764528, 1243.2886940682085

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
139.0, 159.0
829.9775981223105, 1167.545103664102

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
336.0, 27.0
60.0, 34.0

poly I:C

--

e11

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p2

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
222.5, 138.0
31.0, 60.0

CpG DNA: TLR

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p1

p3 p8

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
350.5, 138.0
31.0, 60.0

poly I: C: TLR

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p4

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
447.5, 145.0
37.14397600399933, 45.482419596733884

TCR liagnd: TCR

--

e14

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

p3 p4

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
146.0, 488.0
40.0, 40.0

TGFbeta-receptor

--

e15

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m15

10

false

infinite

0

unit false false false
TRANSPATHMO000061699

--

Go back
146.5, 561.0
31.640559906682213, 38.74354274287619

e16

--

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p6

p8

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
146.5, 684.0
31.91001499750042, 39.07348775204133

e17

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p7

p8

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
130.75, 139.9969080091176
856.2594311764528, 1243.2886940682085

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
147.87518862352903, 157.12209663264667
822.0090539293948, 1209.0383168211513

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
179.55678757705792, 187.09117672382234
758.6458560223374, 1149.1001566387988

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
208.0, 29.5
60.0, 21.0

CpG DNA

--

e5

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
317.0, 593.0
465.6500709748862, 422.29345356567933

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
367.29367619468036, 603.0077409313898
272.27955732982184, 409.2864683429171

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
323.06992643728904, 598.6363602631969
453.51021810030846, 411.0207330392853

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
323.93705878547314, 599.503492611381
451.7759534039399, 409.2864683429171

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
317.0, 593.0
465.6500709748862, 422.29345356567933

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
317.0, 593.0
465.6500709748862, 422.29345356567933

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
323.93705878547314, 599.503492611381
451.7759534039399, 409.2864683429171

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
656.9158804881849, 766.4264696368291
29.091257918298922, 26.33524401024959

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
580.6082338479803, 887.8249983826097
82.37757307749382, 74.57338194383664

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
317.0, 593.0
465.6500709748862, 422.29345356567933

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
444.0, 21.5
44.88576449912126, 29.175746924428825

TCR ligand

--

e6

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p5

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
426.7511016961721, 780.6637213250547
14.746453546866459, 7.100144300343119

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
426.25867587120234, 759.4894108513561
50.4736470593979, 90.85256470691624

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
447.43298634490145, 818.5805098477247
7.878813199515761, 7.8788131995157675

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
142.0, 145.0
839.7237354966342, 1189.8668429177399

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
145.0, 166.0
805.5569854171277, 1169.6687428256696

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
153.0, 187.0
801.8791759029863, 1154.3288303559784

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
223.0, 81.0
30.0, 30.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e5 MO000019395

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c5 : 1
stoichiometry:c2 : 1

m5*m3962*0.1

nodelay

--

true

0

false

PMID: 17888644, 17339441, 15128790, 16761317 In the presence of TCR stimulation, TLR ligands including CpG and PolyI:C enhance proliferation and survival of T cells whilst lowering the threshold required for antigen-induced T cell activation.

Go back
351.0, 85.0
30.0, 30.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e11 MO000019395

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c3 : 1
stoichiometry:c6 : 1
stoichiometry:c4 : 1

m11*m3962*0.1

nodelay

--

true

0

false

PMID: 17888644, 17339441, 15128790, 16761317 In the presence of TCR stimulation, TLR ligands including CpG and PolyI:C enhance proliferation and survival of T cells whilst lowering the threshold required for antigen-induced T cell activation.

Go back
63.0, 213.0
30.0, 30.0

p3

p3

cso30:i:CE_CellProliferation

cso30:i:CC_Extracellular

--

e12 e14

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c12 : 1

m12*m14*0.1

nodelay

--

true

0

false

PMID: 17888644, 17339441, 15128790, 16761317 In the presence of TCR stimulation, TLR ligands including CpG and PolyI:C enhance proliferation and survival of T cells whilst lowering the threshold required for antigen-induced T cell activation.

Go back
67.0, 265.0
30.0, 30.0

p4

p4

cso30:i:CE_CellProliferation

cso30:i:CC_Extracellular

--

e13 e14

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c13 : 1

m13*m14*0.1

nodelay

--

true

0

false

PMID: 17888644, 17339441, 15128790, 16761317 In the presence of TCR stimulation, TLR ligands including CpG and PolyI:C enhance proliferation and survival of T cells whilst lowering the threshold required for antigen-induced T cell activation.

Go back
451.0, 77.0
30.0, 30.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6 MO000017777

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c10 : 1
stoichiometry:c11 : 1

m6*m2534*0.1

nodelay

--

true

0

false

PMID: 17888644, 17339441, 15128790, 16761317 In the presence of TCR stimulation, TLR ligands including CpG and PolyI:C enhance proliferation and survival of T cells whilst lowering the threshold required for antigen-induced T cell activation.

Go back
67.0, 565.0
30.0, 30.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016808 e15

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c15 : 1
stoichiometry:c16 : 1

m1746*m15*0.1

nodelay

--

true

0

false

PMID: 17888644 Indeed, production of IL-17 required simultaneous exposure to CpG and the polarizing cytokines IL-6 and TGF-beta.

Go back
67.0, 689.0
30.0, 30.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000007384 MO000018458

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c21 : 1

m871*m3096*0.1

nodelay

--

true

0

false

PMID: 17888644 Indeed, production of IL-17 required simultaneous exposure to CpG and the polarizing cytokines IL-6 and TGF-beta.

Go back
475.0, 541.0
30.0, 30.0

p8

p8

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G011341 e16 e17 e12

MO000007327

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c24 : 1
stoichiometry:c18 : 1

m94226*m16*m17*m12*0.1

nodelay

--

true

0

false

PMID: 17888644 Indeed, production of IL-17 required simultaneous exposure to CpG and the polarizing cytokines IL-6 and TGF-beta.

Go back
238.0, 51.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
486.77846408158626, 111.5325719930081

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
466.0, 107.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
100.90568189827019, 171.0

c12

c12

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
104.67631553499534, 173.0

c13

c13

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
82.0, 528.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
103.07405281892237, 525.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
97.0, 580.0

c16

c16

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
505.757605382452, 577.4315776466481

c17

c17

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
505.0, 522.5116931692603

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
82.0, 657.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
238.0, 111.0

c2

c2

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
103.23370760249931, 655.0

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
97.0, 704.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
178.0, 557.5909734841225

c22

c22

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
178.0, 566.290062160352

c23

c23

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
254.0, 192.0

c24

c24

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
366.0, 61.0

c3

c3

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
366.0, 115.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
256.3597161657171, 116.93914494038921

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
318.0, 120.89062016604313

c6

c6

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
100.50477179311511, 174.0

c7

c7

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
104.44387268422457, 174.0

c8

c8

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
466.0, 51.0

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back