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Physiological and Pathological Inflammation at the Mucosal Frontline

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Abstract

The intestinal mucosa is covered by a single layer of epithelium, which comprises columnar epithelial cells, goblet cells, Paneth cells, and microfold (M) cells. This tightly associated physical and interactive barrier also provides bactericidal agents, mucins, and fucose to create a symbiotic and protective environment. The initial layers of the mucosal compartment constitutively regulate symbiosis with host and commensal microbiota. This regulation of symbiosis occurs through homeostatic or physiological inflammatory signalling, which is mediated by innate cell populations, including innate lymphoid cells and mast cells. However, damage to the epithelial barrier due to dysbiosis or chemical and physical stressors induces intestinal inflammation (e.g., inflammatory bowel disease [IBD]). The inflamed epithelium then releases damage-associated molecules, such as adenosine triphosphate (ATP), into the extracellular compartment. Extracellular ATP-mediated, purinergic signalling initiates the activation of innate cells (e.g., mast cells) located at the mucosal frontline, which typically function as sentinels against invasion from intestinal infections but also promote the inflammatory process upon its abnormal activation. In this chapter, we discuss these complex mucosal molecular–cellular connections and introduce advanced strategies to control chronic inflammation (e.g., IBD), especially focusing on (1) commensal mutualism, (2) the epithelial barrier, and (3) purinergic inflammatory signalling.

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Acknowledgments

We appreciate our former and current colleagues and collaborators who have been providing their expertise for our understanding of (1) commensal mutualism, (2) the epithelial barrier, and (3) purinergic inflammatory signalling.

Financial Support and Sponsorship

This work was supported by grants from the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency (to H.K.); the Ministry of Education, Science, Sports, and Technology of Japan (MEXT: Grant-in Aid for Scientific Research S [H.K.] and Research Activity Start-up [26893047 to Y.K].); the Young Researcher Overseas Visits Program for Vitalising Brain Circulation (Japan Society for the Promotion of Science, H.K.); and MEXT Translational Research Network Program (at the University of Tokyo) Seeds B and C.

Conflicts of Interest

The authors have no competing interests to report.

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Authors and Affiliations

  1. Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Yosuke Kurashima & Hiroshi Kiyono

  2. International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Hiroshi Kiyono

  3. AMED-CREST, Tokyo, 108-8639, Japan

    Hiroshi Kiyono

  4. Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba, 260-8670, Japan

    Hiroshi Kiyono

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  1. Yosuke Kurashima
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Correspondence to Hiroshi Kiyono .

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  1. Interdisciplinary Program for Biomedical Sciences Institute for Academic Initiatives, Osaka University, Suita, Japan

    Masayuki Miyasaka

  2. Department of Immunobiology and Pharmacological Genetics Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Kiyoshi Takatsu

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Kurashima, Y., Kiyono, H. (2016). Physiological and Pathological Inflammation at the Mucosal Frontline. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_43

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