Attenuation of TNF-driven murine ileitis by intestinal expression of the viral immunomodulator CrmD.
Tumor necrosis factor α (TNFα) is a key pathogenic factor in Crohn's disease and rheumatoid arthritis. TNF(ΔARE) mice express high levels of TNFα and present Crohn's-like ileitis and arthritis. Alterations in the chemokine network could underline the TNF-driven ileitis. The aim of this study was to evaluate the role of TNF and chemokines in ileitis using ectromelia virus cytokine response modifier D (CrmD), a protein that binds TNFα and a limited number of chemokines. We generated transgenic mice expressing CrmD in intestinal epithelial cells (vCrmD mice) and crossed them with the TNF(ΔARE) mice to test whether CrmD could affect TNF-driven inflammatory processes. During homeostasis, only the number of B cells in the lamina propria was reduced by CrmD expression. Interestingly, CrmD expression in the intestine markedly attenuated the inflammatory infiltrates in the ileum of TNF(ΔARE) mice, but did not affect development of arthritis. Our results suggest that CrmD affects development of ileitis by locally affecting both TNF and chemokine function in the ileum.
Viejo-Borbolla
A
A
Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
Martin
A P
AP
Muniz
L R
LR
Shang
L
L
Marchesi
F
F
Thirunarayanan
N
N
Harpaz
N
N
Garcia
R A
RA
Apostolaki
M
M
Furtado
G C
GC
Mayer
L
L
Kollias
G
G
Alcami
A
A
Lira
S A
SA
D000818:Animals; D001168:Arthritis; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004481:Ectromelia virus / Q000276:immunology*; D006801:Humans; D007079:Ileitis; D007249:Inflammation; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012213:Rheumatic Fever / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019076:Transgenes / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D002352:Carrier Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins