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      Guardians of the Gut: Enteric Defensins

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          Abstract

          Enteric defensins likely play a key role in the management of the human microbiome throughout development. The functional and mechanistic diversity of defensins is much greater than was initially thought. Defensin expression and overall Paneth cell physiology likely plays a key role in the development of colitis and other inflammatory or dysbiotic diseases of the gut. As our understanding of enteric defensins grows, their potential as tools of clinical intervention becomes more apparent. In this review, we focus on the function and activity of Paneth Cell defensins and highlight their role in disease.

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          Most cited references66

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          Defensins: antimicrobial peptides of innate immunity.

          Tomas Ganz (2003)
          The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals. Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere. This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins.
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            Graft-versus-host disease.

            Haemopoietic-cell transplantation (HCT) is an intensive therapy used to treat high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. The main complication of HCT is graft-versus-host disease (GVHD), an immunological disorder that affects many organ systems, including the gastrointestinal tract, liver, skin, and lungs. The number of patients with this complication continues to grow, and many return home from transplant centres after HCT requiring continued treatment with immunosuppressive drugs that increases their risks for serious infections and other complications. In this Seminar, we review our understanding of the risk factors and causes of GHVD, the cellular and cytokine networks implicated in its pathophysiology, and current strategies to prevent and treat the disease. We also summarise supportive-care measures that are essential for management of this medically fragile population.
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              Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

              Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                19 April 2017
                2017
                : 8
                : 647
                Affiliations
                Medical Microbiology and Immunology, University of California, Davis Davis, CA, USA
                Author notes

                Edited by: Juarez Antonio Simões Quaresma, Federal University of Pará, Brazil

                Reviewed by: Stephen J. Pandol, Cedars-Sinai Medical Center, USA; Zakee L. Sabree, Ohio State University at Columbus, USA; Jon Y. Takemoto, Utah State University, USA

                *Correspondence: Sumathi Sankaran-Walters ssankaran@ 123456ucdavis.edu

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2017.00647
                5395650
                28469609
                b14c81d1-c274-4e5f-8e20-f3b7f344a110
                Copyright © 2017 Sankaran-Walters, Hart and Dills.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 December 2016
                : 29 March 2017
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 82, Pages: 8, Words: 6874
                Funding
                Funded by: Office of Extramural Research, National Institutes of Health 10.13039/100006955
                Award ID: 1R21HL126562-01A1
                Categories
                Microbiology
                Review

                Microbiology & Virology
                enteric alpha defensins,mucosal immunity,paneth cells,ibd microbiota research,antimicrobial peptide

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