KEGG PATHWAY: cge05332

KEGG

PATHWAY: cge05332

Entry

cge05332                    Pathway

Name

Graft-versus-host disease - Cricetulus griseus (Chinese hamster)

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

Graft-versus-host disease

Organism

Cricetulus griseus (Chinese hamster) [GN:cge]

Gene

Il6; interleukin-6 [KO:K05405]

Il1a; interleukin-1 alpha [KO:K04383]

Il1b; interleukin-1 beta [KO:K04519]

Tnf; tumor necrosis factor isoform X1 [KO:K03156]

H-2 class II histocompatibility antigen, E-S beta chain isoform X2 [KO:K06752]

RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]

HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]

HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]

class II histocompatibility antigen, M alpha chain [KO:K06752]

HLA class II histocompatibility antigen, DO beta chain [KO:K06752]

rano class II histocompatibility antigen, A beta chain isoform X2 [KO:K06752]

H-2 class II histocompatibility antigen, I-E alpha chain [KO:K06752]

LOW QUALITY PROTEIN: H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]

LOW QUALITY PROTEIN: H-2 class II histocompatibility antigen, E-S beta chain-like isoform X2 [KO:K06752]

H-2 class II histocompatibility antigen, E-D beta chain [KO:K06752]

H-2 class II histocompatibility antigen, E-D beta chain-like isoform X2 [KO:K06752]

H-2 class II histocompatibility antigen, E-U alpha chain isoform X2 [KO:K06752]

LOW QUALITY PROTEIN: H-2 class II histocompatibility antigen, E-S beta chain [KO:K06752]

class II histocompatibility antigen, M beta 1 chain [KO:K06752]

T-cell receptor beta-2 chain C region [KO:K10785]

Cd80; T-lymphocyte activation antigen CD80 [KO:K05412]

Cd86; T-lymphocyte activation antigen CD86 isoform X2 [KO:K05413]

Cd28; T-cell-specific surface glycoprotein CD28 [KO:K06470]

Il2; interleukin-2 [KO:K05429]

MHC class I antigen Hm1-C2 precursor [KO:K06751]

MHC class I antigen Hm1-C3 precursor [KO:K06751]

H-2 class I histocompatibility antigen, K-D alpha chain [KO:K06751]

saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]

class I histocompatibility antigen, Gogo-B*0102 alpha chain-like isoform X2 [KO:K06751]

class I histocompatibility antigen, Gogo-B*0102 alpha chain-like [KO:K06751]

class I histocompatibility antigen, Gogo-A*0101 alpha chain-like [KO:K06751]

HLA class I histocompatibility antigen, alpha chain F-like [KO:K06751]

HLA class I histocompatibility antigen, alpha chain F [KO:K06751]

saoe class I histocompatibility antigen, A alpha chain isoform X2 [KO:K06751]

H-2 class I histocompatibility antigen, alpha chain [KO:K06751]

popy Class I histocompatibility antigen, A-1 alpha chain-like isoform X2 [KO:K06751]

patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751]

LOW QUALITY PROTEIN: patr class I histocompatibility antigen, A-126 alpha chain-like isoform X2 [KO:K06751]

RT1 class I histocompatibility antigen, AA alpha chain isoform X2 [KO:K06751]

LOW QUALITY PROTEIN: H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X2 [KO:K06751]

H-2 class I histocompatibility antigen, Q10 alpha chain isoform X2 [KO:K06751]

H-2 class I histocompatibility antigen, Q10 alpha chain isoform X1 [KO:K06751]

H-2 class I histocompatibility antigen, Q10 alpha chain [KO:K06751]

popy Class I histocompatibility antigen, A-1 alpha chain-like [KO:K06751]

MHC class I antigen Hm1-C4 precursor [KO:K06751]

MHC class I antigen Hm1-C5 isoform X1 [KO:K06751]

H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751]

LOW QUALITY PROTEIN: H-2 class I histocompatibility antigen, Q10 alpha chain isoform X2 [KO:K06751]

LOW QUALITY PROTEIN: H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X4 [KO:K06751]

patr class I histocompatibility antigen, A-2 alpha chain [KO:K06751]

RT1 class I histocompatibility antigen, AA alpha chain-like isoform X1 [KO:K06751]

Faslg; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]

Fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]

Prf1; perforin-1 [KO:K07818]

granzyme-like protein 2 [KO:K01353] [EC:3.4.21.79]

granzyme C [KO:K01353] [EC:3.4.21.79]

granzyme B-like [KO:K01353] [EC:3.4.21.79]

granzyme C-like [KO:K01353] [EC:3.4.21.79]

granzyme-like protein 2 [KO:K01353] [EC:3.4.21.79]

granzyme-like protein 2 [KO:K01353] [EC:3.4.21.79]

mast cell protease 8-like [KO:K01353] [EC:3.4.21.79]

granzyme B [KO:K01353] [EC:3.4.21.79]

Ifng; interferon gamma isoform X2 [KO:K04687]

killer cell immunoglobulin-like receptor 3DL1 isoform X2 [KO:K07980]

natural killer cells antigen CD94-like [KO:K06516]

Compound

Lipopolysaccharide

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

Cytokine-cytokine receptor interaction

Apoptosis

Cell adhesion molecules

Antigen processing and presentation

Toll-like receptor signaling pathway

Natural killer cell mediated cytotoxicity

T cell receptor signaling pathway

KO pathway

LinkDB

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