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.

journal_name

Blood

journal_title

Blood

authors

Burman AC,Banovic T,Kuns RD,Clouston AD,Stanley AC,Morris ES,Rowe V,Bofinger H,Skoczylas R,Raffelt N,Fahy O,McColl SR,Engwerda CR,McDonald KP,Hill GR

doi

10.1182/blood-2006-12-063982

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

1064-72

issue

3

eissn

0006-4971

issn

1528-0020

pii

blood-2006-12-063982

journal_volume

110

pub_type

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