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      Effect of the Lactococcus Lactis 11/19-B1 Strain on Atopic Dermatitis in a Clinical Test and Mouse Model

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          Abstract

          Some lactic acid bacteria (LAB) are known to improve atopic dermatitis (AD) through the regulation and stimulation of the host immune system. In this study, we found that ingestion of yogurt containing Lactococcus lactis 11/19-B1 strain ( L. lactis 11/19-B1) daily for 8 weeks significantly improved the severity scoring of atopic dermatitis (SCORAD) system score from 38.8 ± 14.4 to 24.2 ± 12.0 in children suffering from AD. We tried to identify which LAB species among the five species contained in the test yogurt contributed to the improvement in AD pathology using an AD mouse model induced by repeated application of 1-fluoro-2, 4-dinitrobenzene (DNFB). AD-like skin lesions on the dorsal skin and ear were most improved by L. lactis 11/19-B1 intake among the five LAB species. In addition, analysis of CD4+ T cell subsets in Peyer’s patches (PPs) and cervical lymph nodes (CLNs) indicated that the intake of L. lactis 11/19-B1 generally suppressed all subsets related to inflammation, i.e., Th1, Th2 and Th17, instead of activating the suppressive system, Treg, in the AD mouse model. Histological observations showed ingestion of L. lactis 11/19-B1 significantly suppressed severe inflammatory findings, such as inflammatory cell filtration, epidermal erosion and eosinophil infiltration. These results suggest that the immunomodulatory effects of L. lactis 11/19-B1 contribute to improvements in AD pathology.

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          Most cited references37

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          Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function

          Leukocyte traffic through secondary lymphoid tissues is finely tuned by chemokines. We have studied the functional properties of a human T cell subset marked by the expression of CXC chemokine receptor 5 (CXCR5). Memory but not naive T cells from tonsils are CXCR5+ and migrate in response to the B cell–attracting chemokine 1 (BCA-1), which is selectively expressed by reticular cells and blood vessels within B cell follicles. Tonsillar CXCR5+ T cells do not respond to other chemokines present in secondary lymphoid tissues, including secondary lymphoid tissue chemokine (SLC), EBV-induced molecule 1 ligand chemokine (ELC), and stromal cell–derived factor 1 (SDF-1). The involvement of tonsillar CXCR5+ T cells in humoral immune responses is suggested by their localization in the mantle and light zone germinal centers of B cell follicles and by the concomitant expression of activation and costimulatory markers, including CD69, HLA-DR, and inducible costimulator (ICOS). Peripheral blood CXCR5+ T cells also belong to the CD4+ memory T cell subset but, in contrast to tonsillar cells, are in a resting state and migrate weakly to chemokines. CXCR5+ T cells are very inefficient in the production of cytokines but potently induce antibody production during coculture with B cells. These properties portray CXCR5+ T cells as a distinct memory T cell subset with B cell helper function, designated here as follicular B helper T cells (TFH).
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            Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis.

            Assessment methods for atopic dermatitis (AD) are not standardized, and therapeutic studies are difficult to interpret. To obtain a consensus on assessment methods in AD and to use a statistical method to develop a composite severity index. Consensus definitions were given for items used in the scoring system (extent, intensity, subjective) and illustrated for intensity items. Slides were reviewed to address within- and between-observer variability by a group of 10 trained clinicians, and data were statistically evaluated with a two-way analysis of variance. Two variants of an assessment system were compared in 88 patients at 5 different institutions. Data were analyzed using principal-component analysis. For 5 intensity items studied (erythema, edema/papulation, oozing/crusts, excoriations, lichenification), within- and between-observer variability was good overall, except for edema/papulation which was difficult to assess with slides. In the series of 88 patients, principal-component analysis allowed to extract two unrelated components: the first one accounting for 33% of total variance was interpreted as a 'severity' component; the second one, accounting for 18% of variance, was interpreted as a 'profile' component distinguishing patients with mostly erythema and subjective symptoms and those with mostly lichenification and dryness and lower subjective symptoms. Of the two evaluation systems used, the one using the rule of nine to assess extent was found more workable than the one using a distribution x intensity product. A scoring index (SCORAD) combining extent, severity and subjective symptoms was mathematically derived from the first system and showed a normal distribution of the population studied. The final choice for the evaluation system was mostly made based on simplicity and easy routine use in outpatient clinics. Based on mathematical appreciation of weights of the items used in the assessment of AD, extent and subjective symptoms account for around 20% each of the total score, intensity items representing 60%. The so-designed composite index SCORAD needs to be further tested in clinical trials.
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              Possible pathogenic role of Th17 cells for atopic dermatitis.

              The critical role of IL-17 has recently been reported in a variety of conditions. Since IL-17 deeply participates in the pathogenesis of psoriasis and keratinocyte production of certain cytokines, the involvement of T helper cell 17 (Th17) in atopic dermatitis (AD) is an issue to be elucidated. To evaluate the participation of Th17 cells in AD, we successfully detected circulating lymphocytes intracellularly positive for IL-17 by flow cytometry, and the IL-17+ cell population was found exclusively in CD3+CD4+ T cells. The percentage of Th17 cells was increased in peripheral blood of AD patients and associated with severity of AD. There was a significant correlation between the percentages of IL-17+ and IFN-gamma+ cells, although percentage of Th17 cells was not closely related to Th1/Th2 balance. Immunohistochemically, IL-17+ cells infiltrated in the papillary dermis of atopic eczema more markedly in the acute than chronic lesions. Finally, IL-17 stimulated keratinocytes to produce GM-CSF, TNF-alpha, IL-8, CXCL10, and VEGF. A marked synergistic effect between IL-17 and IL-22 was observed on IL-8 production. The number of Th17 cells is increased in the peripheral blood and acute lesional skin of AD. Th17 cells may exaggerate atopic eczema.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                14 March 2020
                March 2020
                : 12
                : 3
                : 763
                Affiliations
                [1 ]Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan; tm1451@ 123456fmu.ac.jp (T.S.); kyoko@ 123456fmu.ac.jp (K.N.)
                [2 ]Laboratory Animal Research Center, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan; kkawata@ 123456fmu.ac.jp
                [3 ]Department of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan; sugikota@ 123456fmu.ac.jp
                [4 ]Isome Children’s Clinic, Fukushima 960-8165, Japan; misome@ 123456cd6.so-net.ne.jp
                [5 ]Department of Pediatrics, Ohara General Hospital, Fukushima 960-8611, Japan; s_shigeo@ 123456ohara-hp.or.jp
                [6 ]Department of Pediatrics, Fujita General Hospital, Kunimi, Date, Fukushima 969-1793, Japan; rurinozawa@ 123456qmail.com
                [7 ]Ichikawa Clinic, Fukushima 960-0112, Japan; i-clinic@ 123456d4.dion.ne.jp
                [8 ]Tohoku Kyodo Milk Co., Ltd., Motomiya, Fukushima 969-1104, Japan; watanabe_zen@ 123456tk-holstein.com
                Author notes
                [* ]Correspondence: suzutani@ 123456fmu.ac.jp ; Tel.: +81-24-547-1158
                Author information
                https://orcid.org/0000-0002-7646-5379
                Article
                nutrients-12-00763
                10.3390/nu12030763
                7146114
                32183266
                9b5b2fd6-8037-4801-80b5-12ec7a6ec9b9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 February 2020
                : 12 March 2020
                Categories
                Article

                Nutrition & Dietetics
                atopic dermatitis,lactococcus lactis,clinical test,mouse model,t cell subsets

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