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The Journal of Immunology, 2008, 180, 2009
Copyright © 2008 by The American Association of Immunologists, Inc.
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Comment on "Resistin-Like Molecule β (RELMβ/FIZZ2) Is Highly Expressed in the Ileum of SAMP1/YitFc Mice and Is Associated with Initiation of Ileitis"

Sicheng Wen*, Christian P. Felley{dagger}, Vera Kessler{dagger}, Pierre Michetti{dagger} and Qiang Pan-Hammarström*

* Division of Clinical Immunology and Transfusion Medicine Department of Laboratory Medicine Karolinska Institutet Stockholm, Sweden {dagger} Division of Gastroenterology and Hepatology Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

Resistin-like molecule β (RELMβ) is an epithelial cell-specific molecule that has been implicated in the defense against intestinal nematode infections in mice (1, 2). Expression of RELMβ also is induced by bacterial colonization in mice (3) and production appears to be restricted to goblet cells in the lung and the intestinal tract (4). Targeted disruption of the gene encoding RELMβ in mice (Retnlb) reduces the severity of acute colitis induced by dextran sodium sulfate (5).

In the November 15, 2007 issue of The Journal of Immunology, Barnes et al. (6) showed that induction of ileal RELMβ expression is associated with the onset and development of inflammation in SAMP1/Fc mice, a murine model of spontaneous chronic ileitis. The authors subsequently suggested that this molecule could be one of the key mediators in the pathogenesis of Crohn’s disease, an inflammatory bowel disease (IBD) in humans.

However, caution should be exercised when extrapolating the function of a given molecule from mice to humans. We have determined RELMβ expression by real-time RT-PCR in a large number of intestinal biopsies obtained from patients with IBD and did not observe any significant difference between patients with Crohn’s disease and controls, nor between patients with ulcerative colitis and controls.

Furthermore, the gene was expressed at a similar level in both endoscopically normal and inflamed mucosa in the patients. Thus, in contrast to its involvement in the IBD-like disease induced in mice, an altered expression level of RELMβ is not associated with IBD in humans.

References

  1. Artis, D.. 2006. New weapons in the war on worms: identification of putative mechanisms of immune-mediated expulsion of gastrointestinal nematodes. Int. J. Parasitol. 36: 723-733. [Medline]
  2. Artis, D., M. L. Wang, S. A. Keilbaugh, W. He, M. Brenes, G. P. Swain, P. A. Knight, D. D. Donaldson, M. A. Lazar, H. R. Miller, et al 2004. RELMβ/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract. Proc. Natl. Acad. Sci. USA 101: 13596-13600. [Abstract/Free Full Text]
  3. He, W., M. L. Wang, H. Q. Jiang, C. M. Steppan, M. E. Shin, M. C. Thurnheer, J. J. Cebra, M. A. Lazar, G. D. Wu. 2003. Bacterial colonization leads to the colonic secretion of RELMβ/FIZZ2, a novel goblet cell-specific protein. Gastroenterology 125: 1388-1397. [Medline]
  4. Zimmermann, N., A. Mishra, N. E. King, P. C. Fulkerson, M. P. Doepker, N. M. Nikolaidis, L. E. Kindinger, E. A. Moulton, B. J. Aronow, M. E. Rothenberg. 2004. Transcript signatures in experimental asthma: identification of STAT6-dependent and -independent pathways. J. Immunol. 172: 1815-1824. [Abstract/Free Full Text]
  5. McVay, L. D., S. A. Keilbaugh, T. M. Wong, S. Kierstein, M. E. Shin, M. Lehrke, M. I. Lefterova, D. E. Shifflett, S. L. Barnes, F. Cominelli, et al 2006. Absence of bacterially induced RELMβ reduces injury in the dextran sodium sulfate model of colitis. J. Clin. Invest. 116: 2914-2923. [Medline]
  6. Barnes, S. L., A. Vidrich, M.-L. Wang, G. D. Wu, F. Cominelli, J. Rivera-Nieves, G. Bamias, S. M. Cohn. 2007. Resistin-like molecule β (RELMβ/FIZZ2) is highly expressed in the ileum of SAMP1/YitFc mice and is associated with initiation of ileitis. J. Immunol. 179: 7012-7020. [Abstract/Free Full Text]



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S. M. Cohn and A. Vidrich
Response to Comment on "Resistin-Like Molecule {beta} (RELM {beta}/FIZZ2) Is Highly Expressed in the Ileum of SAMP1/YitFc Mice and Is Associated with Initiation of Ileitis"
J. Immunol., February 15, 2008; 180(4): 2009 - 2010.
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