International Immunology, Vol. 26, No. 9, pp. 479–480 doi:10.1093/intimm/dxu075

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Introduction: Mucosal Immunology Special Issue Kiyoshi Takeda Associate Editor This Special Issue of review articles focusses on intestinal mucosal immunology to survey our present knowledge of the interplay between the intestinal environmental factors and the mucosal immune system. The figure below is of the intestine and Peyer’s patches, stained for B220 (green), CD4 (red), CD11c (white) and 4′,6-diamidino-2-phenylindole (DAPI; blue). We would like to express our appreciation to the distinguished researchers who contributed to this issue by submitting review articles describing recent progress on the relevant fields comprehensively. We hope the collection of the articles is encouraging and inspiring to all of our readers. Metagenomic analyses of microbiota enabled us to understand how the microbiota establishes the mutual relationship with the intestinal immune system. Mizuho Hasegawa and Naohiro Inohara (p. 481) discuss the mechanisms by which the immune system regulates the microbiota composition.

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Mucosal tissues that are covered by an epithelial cell layer are exposed to the external environment and are vulnerable to invasion by pathogenic micro-organisms. These mucosal tissues are equipped with a specialized immune system—the mucosal immune system—to combat pathogenic micro-organisms. Among the several mucosal tissues in our body, the intestinal tract is unique in that there are huge numbers of ‘nonself’ components that should be eliminated by the immune system. These include the dietary compounds that we ingest and the commensal microbiota that inhabit our intestine. The mucosal immune system in the intestine is unique in that it does not react to these intestinal environmental factors, but establishes a mutual relationship among the components. Imbalanced interaction between the mucosal immune system and the intestinal environmental factors leads to the development of intestinal inflammation.

480  Editorial three populations (groups 1–3), are involved in the maintenance of gut homeostasis or induction of intestinal inflammation depending on the situation. Gregory Sonnenberg (p. 501) provides a comprehensive overview of the functions of ILCs. The intestinal microbiota should be segregated from the intestinal immune system to prevent continuous immune activation. Intestinal epithelial cells play an essential role in the separation of microbiota and the immune cells in the lamina propria. Thus, intestinal epithelial cells establish a barrier in addition to their role in the digestion and absorption of nutrients. The barrier function of the epithelial cells is mediated by modulation of tight junctions as well as the secretion of mucus. Christoph Becker et al. (p. 509) discuss how the barrier function of epithelial cells is maintained by TNF. As discussed above, the mucosal tissues are targets of pathogenic microbes for their invasion of the host. Accordingly, development of effective vaccines that activate the immune system at mucosal surfaces is anticipated for the prevention of infectious diseases. Hiroshi Kiyono et  al. (p. 517) discuss the challenge of developing novel methods for vaccination via mucosal routes.

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They also discuss how pathogenic intestinal bacteria invade the host mucosal tissues. The intestinal microbiota composition is regulated by IgA antibody, as Keiichiro Suzuki and Akira Nakajima (p. 489) discuss. IgA, which is the most predominant antibody in the mucosal immune system, is induced by gut microbiota and then acts in the intestinal lumen for the prevention of pathogenic bacterial invasion as well as the regulation of gut microbiota composition. In addition to adaptive aspects of the immune system, such as IgA, the innate immune system is prerequisite for the regulation of intestinal mucosa. The innate immune system senses microbes via pattern recognition receptors, some of which lead to activation of inflammasomes, and accordingly the innate immune system is critically involved in mucosal immunity through sensing both pathogenic bacteria and commensal microbiota. Richard Flavell et al. (p. 495) discuss the role of inflammasomes in intestinal inflammation and infection. In the intestinal lamina propria, a variety of effector and regulatory immune cell subsets are present. Recently, a new innate subset of cell populations, named innate lymphoid cells (ILCs), has been identified. ILCs, consisting of

Introduction: Mucosal Immunology Special issue.

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