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      Regulation of Allergic Immune Responses by Microbial Metabolites

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          Abstract

          Emerging evidence demonstrates that the microbiota plays an essential role in shaping the development and function of host immune responses. A variety of environmental stimuli, including foods and commensals, are recognized by the host through the epithelium, acting as a physical barrier. Two allergic diseases, atopic dermatitis and food allergy, are closely linked to the microbiota, because inflammatory responses occur on the epidermal border. The microbiota generates metabolites such as short-chain fatty acids and poly-γ-glutamic acid (γPGA), which can modulate host immune responses. Here, we review how microbial metabolites can regulate allergic immune responses. Furthermore, we focus on the effect of γPGA on allergic T helper (Th) 2 responses and its therapeutic application.

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          The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch.

          Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the "atopic march." Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Commensal bacteria protect against food allergen sensitization.

            Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.
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              Commensal bacteria regulate TLR3-dependent inflammation following skin injury

              The normal microflora of the skin includes staphylococcal species that will induce inflammation when present below the dermis but are tolerated on the epidermal surface without initiating inflammation. Here we reveal a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. This inhibition is mediated by staphylococcal lipoteichoic acid (LTA), and acts selectively on keratinocytes triggered through Toll-like receptor (TLR) 3. The significance of this is seen by observations that TLR3 activation is required for normal inflammation after injury, and that keratinocytes require TLR3 to respond to RNA from damaged cells with the release of inflammatory cytokines. Staphylococcal LTA inhibits both inflammatory cytokine release from keratinocytes and inflammation triggered by injury through a TLR2-dependent mechanism. These findings show for the first time that the skin epithelium requires TLR3 for normal inflammation after wounding and that the microflora can modulate specific cutaneous inflammatory responses.
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                Author and article information

                Journal
                Immune Netw
                Immune Netw
                IN
                Immune Network
                The Korean Association of Immunologists
                1598-2629
                2092-6685
                February 2018
                26 February 2018
                : 18
                : 1
                : e15
                Affiliations
                Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Korea.
                Author notes
                Correspondence to Seokmann Hong. Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul 05006, Korea. shong@ 123456sejong.ac.kr
                Article
                10.4110/in.2018.18.e15
                5833122
                29503745
                233e3632-70a5-45a7-bb31-57359e423042
                Copyright © 2018. The Korean Association of Immunologists

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 October 2017
                : 18 February 2018
                : 21 February 2018
                Funding
                Funded by: National Research Foundation of Korea, CrossRef http://dx.doi.org/10.13039/501100003725;
                Award ID: NRF-2016R1D1A1A09919293
                Categories
                Review Article

                Immunology
                microbial metabolites,dermatitis, atopic,food allergy,poly-γ-glutamic acid,inkt cells
                Immunology
                microbial metabolites, dermatitis, atopic, food allergy, poly-γ-glutamic acid, inkt cells

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