KEGG   PATHWAY: mmu05332
Entry
mmu05332                    Pathway                                

Name
Graft-versus-host disease - Mus musculus (mouse)
Description
Graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT) where immunocompetent donor T cells attack the genetically disparate host cells. GVHD pathophysiology can be summerized in a three-step process. Step 1 involves the development of an inflammatory milieu resulting from damage in the host tissues induced by the preparative chemotherapy or radiotherapy regimen. Damaged tissues secrete inflammatory cytokines, including interleukin 1 (IL-1), and tumor necrosis factor (TNF-alpha ). During step 2, antigen-presenting cells (APCs) trigger the activation of donor-derived T cells, which induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B.
Class
Human Diseases; Immune disease
Pathway map
mmu05332  Graft-versus-host disease
mmu05332

Organism
Mus musculus (mouse) [GN:mmu]
Gene
16193  Il6; interleukin 6 [KO:K05405]
16175  Il1a; interleukin 1 alpha [KO:K04383]
16176  Il1b; interleukin 1 beta [KO:K04519]
21926  Tnf; tumor necrosis factor [KO:K03156]
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]
100504404  H2-Ea; histocompatibility 2, class II antigen E alpha [KO:K06752]
381091  H2-Eb2; histocompatibility 2, class II antigen E beta2 [KO:K06752]
12519  Cd80; CD80 antigen [KO:K05412]
12524  Cd86; CD86 antigen [KO:K05413]
12487  Cd28; CD28 antigen [KO:K06470]
16183  Il2; interleukin 2 [KO:K05429]
14990  H2-M2; histocompatibility 2, M region locus 2 [KO:K06751]
14991  H2-M3; histocompatibility 2, M region locus 3 [KO:K06751]
14997  H2-M9; histocompatibility 2, M region locus 9 [KO:K06751]
15006  H2-Q1; histocompatibility 2, Q region locus 1 [KO:K06751]
15007  H2-Q10; histocompatibility 2, Q region locus 10 [KO:K06751]
15013  H2-Q2; histocompatibility 2, Q region locus 2 [KO:K06751]
15018  H2-Q7; histocompatibility 2, Q region locus 7 [KO:K06751]
15019  H2-Q8; histocompatibility 2, Q region locus 8 [KO:K06751]
15039  H2-T22; histocompatibility 2, T region locus 22 [KO:K06751]
15040  H2-T23; histocompatibility 2, T region locus 23 [KO:K06751]
15042  H2-T24; histocompatibility 2, T region locus 24 [KO:K06751]
15043  H2-T3; histocompatibility 2, T region locus 3 [KO:K06751]
15051  H2-T9; histocompatibility 2, T region locus 9 [KO:K06751]
224753  H2-M10.4; histocompatibility 2, M region locus 10.4 [KO:K06751]
224754  H2-M11; histocompatibility 2, M region locus 11 [KO:K06751]
224756  H2-M1; histocompatibility 2, M region locus 1 [KO:K06751]
224761  H2-M10.5; histocompatibility 2, M region locus 10.5 [KO:K06751]
333715  H2-M10.2; histocompatibility 2, M region locus 10.2 [KO:K06751]
399549  H2-M10.6; histocompatibility 2, M region locus 10.6 [KO:K06751]
15024  H2-T10; histocompatibility 2, T region locus 10 [KO:K06751]
110557  H2-Q6; histocompatibility 2, Q region locus 6 [KO:K06751]
110696  H2-M10.3; histocompatibility 2, M region locus 10.3 [KO:K06751]
14963  H2-Bl; histocompatibility 2, blastocyst [KO:K06751]
14964  H2-D1; histocompatibility 2, D region locus 1 [KO:K06751]
14972  H2-K1; histocompatibility 2, K1, K region [KO:K06751]
14985  H2-M10.1; histocompatibility 2, M region locus 10.1 [KO:K06751]
547349  H2-K1; MHC class I family member [KO:K06751]
110558  H2-Q9; histocompatibility 2, Q region locus 9 [KO:K06751]
667977  Gm8909; predicted gene 8909 [KO:K06751]
14980  H2-L; histocompatibility 2, D region locus L [KO:K06751]
69717  Gm10499; predicted gene 10499 [KO:K06751]
15015  H2-Q4; histocompatibility 2, Q region locus 4 [KO:K06751]
667803  H2-T-ps; histocompatibility 2, T region locus, pseudogene [KO:K06751]
100529082  Gm11127; predicted gene 11127 [KO:K06751]
240095  H2-M5; histocompatibility 2, M region locus 5 [KO:K06751]
630294  Gm7030; predicted gene 7030 [KO:K06751]
14103  Fasl; Fas ligand (TNF superfamily, member 6) [KO:K04389]
14102  Fas; Fas (TNF receptor superfamily member 6) [KO:K04390]
18646  Prf1; perforin 1 (pore forming protein) [KO:K07818]
14939  Gzmb; granzyme B [KO:K01353] [EC:3.4.21.79]
15978  Ifng; interferon gamma [KO:K04687]
245616  Kir3dl1; killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1 [KO:K07980]
245615  Kir3dl2; killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 [KO:K07980]
16641  Klrc1; killer cell lectin-like receptor subfamily C, member 1 [KO:K06541]
16643  Klrd1; killer cell lectin-like receptor, subfamily D, member 1 [KO:K06516]
Compound
C00338  Lipopolysaccharide
C00533  Nitric oxide
Reference
  Authors
Ferrara JL, Reddy P.
  Title
Pathophysiology of graft-versus-host disease.
  Journal
Semin Hematol 43:3-10 (2006)
DOI:10.1053/j.seminhematol.2005.09.001
Reference
  Authors
Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease.
  Journal
Hematol Oncol 21:149-61 (2003)
DOI:10.1002/hon.716
Reference
  Authors
Sun Y, Tawara I, Toubai T, Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease: recent advances.
  Journal
Transl Res 150:197-214 (2007)
DOI:10.1016/j.trsl.2007.06.003
Reference
  Authors
Jaksch M, Mattsson J.
  Title
The pathophysiology of acute graft-versus-host disease.
  Journal
Scand J Immunol 61:398-409 (2005)
DOI:10.1111/j.1365-3083.2005.01595.x
Reference
  Authors
Vogelsang GB, Lee L, Bensen-Kennedy DM.
  Title
Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant.
  Journal
Annu Rev Med 54:29-52 (2003)
DOI:10.1146/annurev.med.54.101601.152339
Reference
  Authors
Reddy P, Ferrara JL.
  Title
Immunobiology of acute graft-versus-host disease.
  Journal
Blood Rev 17:187-94 (2003)
DOI:10.1016/S0268-960X(03)00009-2
Reference
  Authors
Blazar BR, Murphy WJ.
  Title
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
  Journal
Philos Trans R Soc Lond B Biol Sci 360:1747-67 (2005)
DOI:10.1098/rstb.2005.1701
Reference
  Authors
Couriel D, Caldera H, Champlin R, Komanduri K.
  Title
Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management.
  Journal
Cancer 101:1936-46 (2004)
DOI:10.1002/cncr.20613
Reference
  Authors
Jacobsohn DA, Vogelsang GB.
  Title
Acute graft versus host disease.
  Journal
Orphanet J Rare Dis 2:35 (2007)
DOI:10.1186/1750-1172-2-35
Related
pathway
mmu04060  Cytokine-cytokine receptor interaction
mmu04210  Apoptosis
mmu04514  Cell adhesion molecules
mmu04612  Antigen processing and presentation
mmu04620  Toll-like receptor signaling pathway
mmu04650  Natural killer cell mediated cytotoxicity
mmu04660  T cell receptor signaling pathway
KO pathway
ko05332   

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