PATHWAY: mmu05332 Help
Entry
Name
Graft-versus-host disease - Mus musculus (house 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
BRITE hierarchy
Pathway map
Disease
H00084 Graft-versus-host disease
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
100504404 H2-Ea; histocompatibility 2, class II antigen E alpha [KO:K06752 ]
110557 H2-Q6; histocompatibility 2, Q region locus 6 [KO:K06751 ]
110558 H2-Q9; histocompatibility 2, Q region locus 9 [KO:K06751 ]
110696 H2-M10.3; histocompatibility 2, M region locus 10.3 [KO:K06751 ]
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 ]
14963 H2-Bl; histocompatibility 2, blastocyst [KO:K06751 ]
14964 H2-D1; histocompatibility 2, D region locus 1 [KO:K06751 ]
14969 H2-Eb1; histocompatibility 2, class II antigen E beta [KO:K06752 ]
14972 H2-K1; histocompatibility 2, K1, K region [KO:K06751 ]
14980 H2-L; histocompatibility 2, D region locus L [KO:K06751 ]
14985 H2-M10.1; histocompatibility 2, M region locus 10.1 [KO:K06751 ]
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 ]
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 ]
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 ]
15015 H2-Q4; histocompatibility 2, Q region locus 4 [KO:K06751 ]
15018 H2-Q7; histocompatibility 2, Q region locus 7 [KO:K06751 ]
15024 H2-T10; histocompatibility 2, T region locus 10 [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 ]
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 ]
18646 Prf1; perforin 1 (pore forming protein) [KO:K07818 ]
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 ]
240095 H2-M5; histocompatibility 2, M region locus 5 [KO:K06751 ]
245615 Kir3dl2; killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 [KO:K07980 ]
245616 Kir3dl1; killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1 [KO:K07980 ]
333715 H2-M10.2; histocompatibility 2, M region locus 10.2 [KO:K06751 ]
381091 H2-Eb2; histocompatibility 2, class II antigen E beta2 [KO:K06752 ]
399549 H2-M10.6; histocompatibility 2, M region locus 10.6 [KO:K06751 ]
630294 H2-T25; histocompatibility-2, T region locus 25 [KO:K06751 ]
667977 H2-T26; histocompatibility 2, T region locus 26 [KO:K06751 ]
Compound
Reference
Authors
Ferrara JL, Reddy P.
Title
Pathophysiology of graft-versus-host disease.
Journal
Reference
Authors
Reddy P.
Title
Pathophysiology of acute graft-versus-host disease.
Journal
Reference
Authors
Sun Y, Tawara I, Toubai T, Reddy P.
Title
Pathophysiology of acute graft-versus-host disease: recent advances.
Journal
Reference
Authors
Jaksch M, Mattsson J.
Title
The pathophysiology of acute graft-versus-host disease.
Journal
Reference
Authors
Vogelsang GB, Lee L, Bensen-Kennedy DM.
Title
Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant.
Journal
Reference
Authors
Reddy P, Ferrara JL.
Title
Immunobiology of acute graft-versus-host disease.
Journal
Reference
Authors
Blazar BR, Murphy WJ.
Title
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
Journal
Reference
Authors
Couriel D, Caldera H, Champlin R, Komanduri K.
Title
Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management.
Journal
Reference
Authors
Jacobsohn DA, Vogelsang GB.
Title
Acute graft versus host disease.
Journal
Related pathway
mmu04060 Cytokine-cytokine receptor interaction
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
All links
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