Development of chronic colitis is dependent on the cytokine MIF.
The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease.
de Jong
Y P
YP
Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Abadia-Molina
A C
AC
Satoskar
A R
AR
Clarke
K
K
Rietdijk
S T
ST
Faubion
W A
WA
Mizoguchi
E
E
Metz
C N
CN
Alsahli
M
M
ten Hove
T
T
Keates
A C
AC
Lubetsky
J B
JB
Farrell
R J
RJ
Michetti
P
P
van Deventer
S J
SJ
Lolis
E
E
David
J R
JR
Bhan
A K
AK
Terhorst
C
C
Sahli
M A
MA
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy; D003424:Crohn Disease / Q000097:blood* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009687:Nuclear Proteins; D011828:Radiation Chimera; D015431:Weight Loss
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2