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Development of chronic colitis is dependent on the cytokine MIF

A Correction to this article was published on 01 April 2002

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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Figure 1: MIF plasma concentrations in patients with Crohn's disease decrease after successful treatment.
Figure 2: MIF-deficient mice do not develop severe colitis.
Figure 3: Experimental colitis depends on MIF produced by non-T hematopoietic cells.
Figure 4: Differences in colon pathology between MIF−/−RAG-2−/− and RAG-2−/− mice after the introduction of colitis-inducing T cells.
Figure 5: Anti-MIF therapy can abrogate the development of experimental colitis.
Figure 6: MIF induces IL-6 and IL-12 production in macrophages.

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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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Correspondence to Cox Terhorst.

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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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