title: IFNgamma differentially controls the development of idiopathic pneumonia syndrome and GVHD of the gastrointestinal tract.
abstract: Although proinflammatory cytokines are key mediators of tissue damage during graft-versus-host disease (GVHD), IFNgamma has previously been attributed with both protective and pathogenic effects. We have resolved this paradox by using wild-type (wt), IFNgamma(-/-), and IFNgammaR(-/-) mice as donors or recipients in well-described models of allogeneic stem cell transplantation (SCT). We show that donor-derived IFNgamma augments acute GVHD via direct effects on (1) the donor T cell to promote T helper 1 (Th1) differentiation and (2) the gastrointestinal (GI) tract to augment inflammatory cytokine generation. However, these detrimental effects are overwhelmed by a protective role of IFNgamma in preventing the development of idiopathic pneumonia syndrome (IPS). This is the result of direct effects on pulmonary parenchyma to prevent donor cell migration and expansion within the lung. Thus, IFNgamma is the key cytokine differentially controlling the development of IPS and gastrointestinal GVHD after allogeneic SCT.
authors: Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4006, Australia.
authors: Angela C
authors: AC
authors: Burman
authors: Tatjana
authors: T
authors: Banovic
authors: Rachel D
authors: RD
authors: Kuns
authors: Andrew D
authors: AD
authors: Clouston
authors: Amanda C
authors: AC
authors: Stanley
authors: Edward S
authors: ES
authors: Morris
authors: Vanessa
authors: V
authors: Rowe
authors: Helen
authors: H
authors: Bofinger
authors: Renae
authors: R
authors: Skoczylas
authors: Neil
authors: N
authors: Raffelt
authors: Olivier
authors: O
authors: Fahy
authors: Shaun R
authors: SR
authors: McColl
authors: Christian R
authors: CR
authors: Engwerda
authors: Kelli P A
authors: KP
authors: McDonald
authors: Geoffrey R
authors: GR
authors: Hill
mesh_terms: D000208:Acute Disease; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D041981:Gastrointestinal Tract / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D033581:Stem Cell Transplantation; D013577:Syndrome; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D007371:Interferon-gamma