Abstract
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.
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Acknowledgements
We thank D. Podolsky for critically reviewing the manuscript, A. Meinhardt for technical advice and G. Lin for assistance with genotyping mice. Supported by grants from the National Institutes of Health (DK52510 to C. T.; DK47677 to A. K. B.; AI25532 to J. R. D.; DK43351 to C. T. and A. K. B.) and the Crohn's and Colitis Foundation of America (Y. P. J.).
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de Jong, Y., Abadia-Molina, A., Satoskar, A. et al. Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol 2, 1061–1066 (2001). https://doi.org/10.1038/ni720
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DOI: https://doi.org/10.1038/ni720
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