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GAITing the GUT

Cellular & Molecular Immunology volume 15, pages 1082–1084 (2018)Cite this article

The gastrointestinal tract contains one of the most abundant populations of macrophages in the body.1 These cells play a critical role in the maintenance of gut homeostasis and defend the integrity of epithelial crypts and the mucosal membrane. Chronic disruption of gut homeostasis can cause sustained inflammation mediated by intestinal macrophages. Since inflammation plays a key role in ulcerative colitis (UC) and other forms of inflammatory bowel disease (IBD),2,3,4 an improved understanding of how inflammation is regulated in the gut is essential for the development of effective therapies for such diseases.

Intestinal homeostasis is maintained by a population of resident macrophages that is sustained through recruitment of circulating monocytes (precursors of macrophages) as well as migration of macrophages from the lymphatic system to target mucosal tissues. These processes are driven by the concerted action of an array of chemokines and chemokine receptors.5, 6 In addition, the diverse microorganisms that densely populate the intestine continuously attract macrophages. Macrophages may encounter commensal microorganisms in the draining lymph nodes or during occasional compromise of the gut epithelial barrier.7, 8 Macrophages have diverse and plastic phenotypes and undergo a series of changes during their response, which is spatially and temporally regulated by multiple and often self-limiting signals. Several intermediate phenotypes between the so-called classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory) phenotypes have been identified.9, 10 A surprising characteristic of intestinal macrophages is their ability to maintain a noninflammatory state. As shown by many studies, this noninflammatory state is maintained through downregulation of diverse molecules involved in the innate immune response of intestinal macrophages.11 However, whether macrophages resolve intestinal inflammation by triggering a single mechanism that targets a cohort of inflammatory genes, or whether this is achieved through the concerted action of several mechanisms was previously unknown.

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References

  1. Lee, S. H., Starkey, P. M. & Gordon, S. Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80. J. Exp. Med. 161, 475–489 (1985).

    Article  CAS  Google Scholar 

  2. Zigmond, E. & Jung, S. Intestinal macrophages: well educated exceptions from the rule. Trends Immunol. 34, 162–168 (2013).

    Article  CAS  Google Scholar 

  3. Xavier, R. J. & Podolsky, D. K. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427–434 (2007).

    Article  CAS  Google Scholar 

  4. Mowat, A. M. & Bain, C. C. Mucosal macrophages in intestinal homeostasis and inflammation. J. Innate Immun. 3, 550–564 (2011).

    Article  Google Scholar 

  5. Varol, C. et al. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31, 502–512 (2009).

    Article  CAS  Google Scholar 

  6. Bogunovic, M. et al. Origin of the lamina propria dendritic cell network. Immunity 31, 513–525 (2009).

    Article  CAS  Google Scholar 

  7. Berg, R. D. Bacterial translocation from the gastrointestinal tract. Trends Microbiol. 3, 149–154 (1995).

    Article  CAS  Google Scholar 

  8. Hooper, L. V. & Macpherson, A. J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10, 159–169 (2010).

    Article  CAS  Google Scholar 

  9. Galli, S. J., Borregaard, N. & Wynn, T. A. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat. Immunol. 12, 1035–1044 (2011).

    Article  CAS  Google Scholar 

  10. Mills, C. D. & Ley, K. M1 and M2 macrophages: the chicken and the egg of immunity. J. Innate Immun. 6, 716–726 (2014).

    Article  CAS  Google Scholar 

  11. Smith, P. D. et al. Intestinal macrophages and response to microbial encroachment. Mucosal Immunol. 4, 31–42 (2011).

    Article  Google Scholar 

  12. Poddar, D., Kaur, R., Baldwin, W. M. 3rd & Mazumder, B. L13a-dependent translational control in macrophages limits the pathogenesis of colitis. Cell. Mol. Immunol. 13, 816–827 (2016).

    Article  CAS  Google Scholar 

  13. Mazumder, B. & Fox, P. L. Delayed translational silencing of ceruloplasmin transcript in gamma interferon-activated U937 monocytic cells: role of the 3’ untranslated region. Mol. Cell. Biol. 19, 6898–6905 (1999).

    Article  CAS  Google Scholar 

  14. Vyas, K. et al. Genome-wide polysome profiling reveals an inflammation-responsive posttranscriptional operon in gamma interferon-activated monocytes. Mol. Cell. Biol. 29, 458–470 (2009).

    Article  CAS  Google Scholar 

  15. Kapasi, P. et al. L13a blocks 48S assembly: role of a general initiation factor in mRNA-specific translational control. Mol. Cell 25, 113–126 (2007).

    Article  CAS  Google Scholar 

  16. Poddar, D. et al. An extraribosomal function of ribosomal protein L13a in macrophages resolves inflammation. J. Immunol. 190, 3600–3612 (2013).

    Article  CAS  Google Scholar 

  17. Basu, A. et al. Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by limiting translation control-dependent retardation of inflammation. Arterioscler. Thromb. Vasc. Biol. 34, 533–542 (2014).

    Article  CAS  Google Scholar 

  18. Cario, E. et al. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J. Immunol. 164, 966–972 (2000).

    Article  CAS  Google Scholar 

  19. Hisamatsu, T. et al. CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology 124, 993–1000 (2003).

    Article  CAS  Google Scholar 

  20. Basu, A., Jain, N., Tolbert, B. S., Komar, A. A. & Mazumder, B. Conserved structures formed by heterogeneous RNA sequences drive silencing of an inflammation responsive post-transcriptional operon. Nucleic Acids Res. 45, 12987–13003 (2017).

    Article  CAS  Google Scholar 

  21. Okayasu, I. et al. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98, 694–702 (1990).

    Article  CAS  Google Scholar 

  22. Merker, S. R., Weitz, J. & Stange, D. E. Gastrointestinal organoids: how they gut it out. Dev. Biol. 420, 239–250 (2016).

    Article  CAS  Google Scholar 

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Acknowledgements

The author would like to thank Dr. Anton Komar and Dr. Aaron Severson for their valuable comments on this manuscript and Dr. Patricia Stanhope Baker for assistance with manuscript editing. Research in the author’s laboratory was funded by the National Institute of Health (NIH) Public Health Service Grant No. HL 079164. The author also received financial assistance from the Center for Gene Regulation in Health & Disease of Cleveland State University and Ohio Third Frontier Grant.

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  1. Center for Gene Regulation in Health and Disease, Department of Biology, Geology and Environmental Sciences, Cleveland State University, Cleveland, OH, USA

    Barsanjit Mazumder

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Correspondence to Barsanjit Mazumder.

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Mazumder, B. GAITing the GUT. Cell Mol Immunol 15, 1082–1084 (2018). https://doi.org/10.1038/s41423-018-0039-6

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