KEGG   PATHWAY: mmu05323
Entry
mmu05323                    Pathway                                
Name
Rheumatoid arthritis - Mus musculus (house mouse)
Description
Rheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune system elevates pro-inflammatory cytokines and chemokines levels, which can promote synovial angiogenesis and leukocyte infiltration. The synovium forms a hyperplastic pannus with infiltrated macrophage-like and fibroblast-like synoviocytes and invades joints by secreting proteinases and inducing osteoclast differentiation.
Class
Human Diseases; Immune disease
Pathway map
mmu05323  Rheumatoid arthritis
mmu05323

Disease
H00630  Rheumatoid arthritis
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
100504404  H2-Ea; histocompatibility 2, class II antigen E alpha [KO:K06752]
108664  Atp6v1h; ATPase, H+ transporting, lysosomal V1 subunit H [KO:K02144]
110935  Atp6v1b1; ATPase, H+ transporting, lysosomal V1 subunit B1 [KO:K02147]
114143  Atp6v0b; ATPase, H+ transporting, lysosomal V0 subunit B [KO:K03661]
11433  Acp5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]
11600  Angpt1; angiopoietin 1 [KO:K05465]
11964  Atp6v1a; ATPase, H+ transporting, lysosomal V1 subunit A [KO:K02145] [EC:7.1.2.2]
11966  Atp6v1b2; ATPase, H+ transporting, lysosomal V1 subunit B2 [KO:K02147]
11972  Atp6v0d1; ATPase, H+ transporting, lysosomal V0 subunit D1 [KO:K02146]
11973  Atp6v1e1; ATPase, H+ transporting, lysosomal V1 subunit E1 [KO:K02150]
11974  Atp6v0e; ATPase, H+ transporting, lysosomal V0 subunit E [KO:K02153]
11975  Atp6v0a1; ATPase, H+ transporting, lysosomal V0 subunit A1 [KO:K02154]
11984  Atp6v0c; ATPase, H+ transporting, lysosomal V0 subunit C [KO:K02155]
12477  Ctla4; cytotoxic T-lymphocyte-associated protein 4 [KO:K06538]
12487  Cd28; CD28 antigen [KO:K06470]
12519  Cd80; CD80 antigen [KO:K05412]
12524  Cd86; CD86 antigen [KO:K05413]
12977  Csf1; colony stimulating factor 1 (macrophage) [KO:K05453]
12981  Csf2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
13038  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
13039  Ctsl; cathepsin L [KO:K01365] [EC:3.4.22.15]
140494  Atp6v0a4; ATPase, H+ transporting, lysosomal V0 subunit A4 [KO:K02154]
14254  Flt1; FMS-like tyrosine kinase 1 [KO:K05096] [EC:2.7.10.1]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
14825  Cxcl1; C-X-C motif chemokine ligand 1 [KO:K05505]
14960  H2-Aa; histocompatibility 2, class II antigen A, alpha [KO:K06752]
14961  H2-Ab1; histocompatibility 2, class II antigen A, beta 1 [KO:K06752]
14969  H2-Eb1; histocompatibility 2, class II antigen E beta [KO:K06752]
14998  H2-DMa; histocompatibility 2, class II, locus DMa [KO:K06752]
14999  H2-DMb1; histocompatibility 2, class II, locus Mb1 [KO:K06752]
15000  H2-DMb2; histocompatibility 2, class II, locus Mb2 [KO:K06752]
15001  H2-Oa; histocompatibility 2, O region alpha locus [KO:K06752]
15002  H2-Ob; histocompatibility 2, O region beta locus [KO:K06752]
15894  Icam1; intercellular adhesion molecule 1 [KO:K06490]
15978  Ifng; interferon gamma [KO:K04687]
16156  Il11; interleukin 11 [KO:K05417]
16168  Il15; interleukin 15 [KO:K05433]
16171  Il17a; interleukin 17A [KO:K05489]
16173  Il18; interleukin 18 [KO:K05482]
16175  Il1a; interleukin 1 alpha [KO:K04383]
16176  Il1b; interleukin 1 beta [KO:K04519]
16193  Il6; interleukin 6 [KO:K05405]
16408  Itgal; integrin alpha L [KO:K05718]
16414  Itgb2; integrin beta 2 [KO:K06464]
16415  Itgb2l; integrin beta 2-like [KO:K06464]
16476  Jun; jun proto-oncogene [KO:K04448]
16994  Ltb; lymphotoxin B [KO:K03157]
17392  Mmp3; matrix metallopeptidase 3 [KO:K01394] [EC:3.4.24.17]
19226  Pth; parathyroid hormone [KO:K05261]
20293  Ccl12; C-C motif chemokine ligand 12 [KO:K14624]
20296  Ccl2; C-C motif chemokine ligand 2 [KO:K14624]
20297  Ccl20; C-C motif chemokine ligand 20 [KO:K14625]
20302  Ccl3; C-C motif chemokine ligand 3 [KO:K05408]
20304  Ccl5; C-C motif chemokine ligand 5 [KO:K12499]
20310  Cxcl2; C-X-C motif chemokine ligand 2 [KO:K05505]
20311  Cxcl5; C-X-C motif chemokine ligand 5 [KO:K05506]
20315  Cxcl12; C-X-C motif chemokine ligand 12 [KO:K10031]
21687  Tek; TEK receptor tyrosine kinase [KO:K05121] [EC:2.7.10.1]
21803  Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21809  Tgfb3; transforming growth factor, beta 3 [KO:K13377]
21871  Atp6v0a2; ATPase, H+ transporting, lysosomal V0 subunit A2 [KO:K02154]
21898  Tlr4; toll-like receptor 4 [KO:K10160]
21926  Tnf; tumor necrosis factor [KO:K03156]
21934  Tnfrsf11a; tumor necrosis factor receptor superfamily, member 11a, NFKB activator [KO:K05147]
21943  Tnfsf11; tumor necrosis factor (ligand) superfamily, member 11 [KO:K05473]
22339  Vegfa; vascular endothelial growth factor A [KO:K05448]
24088  Tlr2; toll-like receptor 2 [KO:K10159]
24099  Tnfsf13b; tumor necrosis factor (ligand) superfamily, member 13b [KO:K05476]
242341  Atp6v0d2; ATPase, H+ transporting, lysosomal V0 subunit D2 [KO:K02146]
27060  Tcirg1; T cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein A3 [KO:K02154]
330122  Cxcl3; C-X-C motif chemokine ligand 3 [KO:K05505]
338375  Atp6v1g3; ATPase, H+ transporting, lysosomal V1 subunit G3 [KO:K02152]
381091  H2-Eb2; histocompatibility 2, class II antigen E beta2 [KO:K06752]
54411  Atp6ap1; ATPase, H+ transporting, lysosomal accessory protein 1 [KO:K03662]
66144  Atp6v1f; ATPase, H+ transporting, lysosomal V1 subunit F [KO:K02151]
66237  Atp6v1g2; ATPase, H+ transporting, lysosomal V1 subunit G2 [KO:K02152]
66290  Atp6v1g1; ATPase, H+ transporting, lysosomal V1 subunit G1 [KO:K02152]
66335  Atp6v1c1; ATPase, H+ transporting, lysosomal V1 subunit C1 [KO:K02148]
68775  Atp6v1c2; ATPase, H+ transporting, lysosomal V1 subunit C2 [KO:K02148]
69583  Tnfsf13; tumor necrosis factor (ligand) superfamily, member 13 [KO:K05475]
73834  Atp6v1d; ATPase, H+ transporting, lysosomal V1 subunit D [KO:K02149]
74915  Atp6v1e2; ATPase, H+ transporting, lysosomal V1 subunit E2 [KO:K02150]
76252  Atp6v0e2; ATPase, H+ transporting, lysosomal V0 subunit E2 [KO:K02153]
83430  Il23a; interleukin 23, alpha subunit p19 [KO:K05426]
83995  Mmp1a; matrix metallopeptidase 1a (interstitial collagenase) [KO:K01388] [EC:3.4.24.7]
83996  Mmp1b; matrix metallopeptidase 1b (interstitial collagenase) [KO:K01388] [EC:3.4.24.7]
Compound
C00080  H+
C00584  Prostaglandin E2
C05443  Vitamin D3
Reference
PMID:16127012
  Authors
Zwerina J, Redlich K, Schett G, Smolen JS
  Title
Pathogenesis of rheumatoid arthritis: targeting cytokines.
  Journal
Ann N Y Acad Sci 1051:716-29 (2005)
DOI:10.1196/annals.1361.116
Reference
PMID:20036936
  Authors
Szekanecz Z, Vegvari A, Szabo Z, Koch AE
  Title
Chemokines and chemokine receptors in arthritis.
  Journal
Front Biosci (Schol Ed) 2:153-67 (2010)
DOI:10.2741/53
Reference
PMID:20651747
  Authors
Isaacs JD
  Title
The changing face of rheumatoid arthritis: sustained remission for all?
  Journal
Nat Rev Immunol 10:605-11 (2010)
DOI:10.1038/nri2804
Reference
PMID:17195034
  Authors
Strand V, Kimberly R, Isaacs JD
  Title
Biologic therapies in rheumatology: lessons learned, future directions.
  Journal
Nat Rev Drug Discov 6:75-92 (2007)
DOI:10.1038/nrd2196
Reference
PMID:20193003
  Authors
Bartok B, Firestein GS
  Title
Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis.
  Journal
Immunol Rev 233:233-55 (2010)
DOI:10.1111/j.0105-2896.2009.00859.x
Reference
PMID:17502360
  Authors
Dai SM, Shan ZZ, Xu H, Nishioka K
  Title
Cellular targets of interleukin-18 in rheumatoid arthritis.
  Journal
Ann Rheum Dis 66:1411-8 (2007)
DOI:10.1136/ard.2006.067793
Reference
PMID:9627005
  Authors
Koch AE
  Title
Review: angiogenesis: implications for rheumatoid arthritis.
  Journal
Arthritis Rheum 41:951-62 (1998)
DOI:10.1002/1529-0131(199806)41:6<951::AID-ART2>3.0.CO;2-D
Reference
PMID:20305562
  Authors
Szekanecz Z, Besenyei T, Szentpetery A, Koch AE
  Title
Angiogenesis and vasculogenesis in rheumatoid arthritis.
  Journal
Curr Opin Rheumatol 22:299-306 (2010)
DOI:10.1097/BOR.0b013e328337c95a
Reference
PMID:15059264
  Authors
Brunner-Weinzierl MC, Hoff H, Burmester GR
  Title
Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases.
  Journal
Arthritis Res Ther 6:45-54 (2004)
DOI:10.1186/ar1158
Reference
PMID:11861618
  Authors
Theill LE, Boyle WJ, Penninger JM
  Title
RANK-L and RANK: T cells, bone loss, and mammalian evolution.
  Journal
Annu Rev Immunol 20:795-823 (2002)
DOI:10.1146/annurev.immunol.20.100301.064753
Reference
PMID:19184540
  Authors
Mensah KA, Li J, Schwarz EM
  Title
The emerging field of osteoimmunology.
  Journal
Immunol Res 45:100-13 (2009)
DOI:10.1007/s12026-009-8093-x
Reference
PMID:16313349
  Authors
Takayanagi H, Sato K, Takaoka A, Taniguchi T
  Title
Interplay between interferon and other cytokine systems in bone metabolism.
  Journal
Immunol Rev 208:181-93 (2005)
DOI:10.1111/j.0105-2896.2005.00337.x
Reference
PMID:20392226
  Authors
Takayanagi H
  Title
New immune connections in osteoclast formation.
  Journal
Ann N Y Acad Sci 1192:117-23 (2010)
DOI:10.1111/j.1749-6632.2009.05303.x
Reference
PMID:19585227
  Authors
Nakashima T, Takayanagi H
  Title
Osteoimmunology: crosstalk between the immune and bone systems.
  Journal
J Clin Immunol 29:555-67 (2009)
DOI:10.1007/s10875-009-9316-6
Reference
PMID:19455385
  Authors
Nakashima T, Takayanagi H
  Title
Osteoclasts and the immune system.
  Journal
J Bone Miner Metab 27:519-29 (2009)
DOI:10.1007/s00774-009-0089-z
Reference
PMID:17380158
  Authors
Takayanagi H
  Title
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
  Journal
Nat Rev Immunol 7:292-304 (2007)
DOI:10.1038/nri2062
Reference
PMID:20510236
  Authors
Fox DA, Gizinski A, Morgan R, Lundy SK
  Title
Cell-cell interactions in rheumatoid arthritis synovium.
  Journal
Rheum Dis Clin North Am 36:311-23 (2010)
DOI:10.1016/j.rdc.2010.02.004
Reference
PMID:15055519
  Authors
Rho J, Takami M, Choi Y
  Title
Osteoimmunology: interactions of the immune and skeletal systems.
  Journal
Mol Cells 17:1-9 (2004)
Related
pathway
mmu04370  VEGF signaling pathway
mmu04380  Osteoclast differentiation
mmu04620  Toll-like receptor signaling pathway
mmu04659  Th17 cell differentiation
mmu04660  T cell receptor signaling pathway
mmu04670  Leukocyte transendothelial migration
KO pathway
ko05323   

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