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      Characterization of the human immune cell network at the gingival barrier

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          Abstract

          The oral mucosa is a barrier site constantly exposed to rich and diverse commensal microbial communities, yet little is known of the immune cell network maintaining immune homeostasis at this interface. We have performed a detailed characterization of the immune cell subsets of the oral cavity in a large cohort of healthy subjects. We focused our characterization on the gingival interface, a particularly vulnerable mucosal site, with thin epithelial lining and constant exposure to the tooth adherent biofilm. In health, we find a predominance of T cells, minimal B cells, a large presence of granulocytes/neutrophils, a sophisticated network of professional antigen presenting cells (APC) and a small population of innate lymphoid cells (ILC) policing the gingival barrier. We further characterize cellular subtypes in health and interrogate shifts in immune cell populations in the common oral inflammatory disease periodontitis. In disease we document an increase in neutrophils and an up regulation of IL-17 responses. We identify the main source of IL-17 in health and periodontitis within the CD4 + T cell compartment. Collectively our studies provide a first view of the landscape of physiologic oral immunity and serve as a baseline for the characterization of local immunopathology.

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          Most cited references29

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          Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection.

          We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab labeling, and expressed elevated levels of CD69 and CD11a compared with those of circulating memory populations. Importantly, influenza-specific lung-resident memory CD4 T cells served as in situ protectors to respiratory viral challenge, mediating enhanced viral clearance and survival to lethal influenza infection. By contrast, memory CD4 T cells isolated from spleen recirculated among multiple tissues without retention and failed to mediate protection to influenza infection, despite their ability to expand and migrate to the lung. Our results reveal tissue compartmentalization as a major determining factor for immune-mediated protection in a key mucosal site, important for targeting local protective responses in vaccines and immunotherapies.
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            Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells.

            Little is known about the functional differences between the human skin myeloid dendritic cell (DC) subsets, epidermal CD207(+) Langerhans cells (LCs) and dermal CD14(+) DCs. We showed that CD14(+) DCs primed CD4(+) T cells into cells that induce naive B cells to switch isotype and become plasma cells. In contrast, LCs preferentially induced the differentiation of CD4(+) T cells secreting T helper 2 (Th2) cell cytokines and were efficient at priming and crosspriming naive CD8(+) T cells. A third DC population, CD14(-)CD207(-)CD1a(+) DC, which resides in the dermis, could activate CD8(+) T cells better than CD14(+) DCs but less efficiently than LCs. Thus, the human skin displays three DC subsets, two of which, i.e., CD14(+) DCs and LCs, display functional specializations, the preferential activation of humoral and cellular immunity, respectively.
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              Compartmentalized and systemic control of tissue immunity by commensals.

              The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective, we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology.
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                Author and article information

                Journal
                101299742
                35518
                Mucosal Immunol
                Mucosal Immunol
                Mucosal immunology
                1933-0219
                1935-3456
                2 December 2015
                06 January 2016
                September 2016
                17 August 2016
                : 9
                : 5
                : 1163-1172
                Affiliations
                [1 ]Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, MD, USA
                [2 ]Manchester Immunology Group, Faculty of Life Sciences, University of Manchester, Manchester, UK
                Author notes
                Correspondence: Niki M. Moutsopoulos, 30 Convent Dr., Bethesda, MD 20892, Tel:301-4357182, nmoutsop@ 123456mail.nih.gov
                Article
                NIHMS741496
                10.1038/mi.2015.136
                4820049
                26732676
                8a5c94b2-aed7-42e2-b389-38a165d242c2

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Article

                Immunology
                oral immunity,oral barrier,oral mucosa,periodontitis,th17
                Immunology
                oral immunity, oral barrier, oral mucosa, periodontitis, th17

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