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      Seasonal variation in circulating group 2 innate lymphoid cells in mugwort-allergic asthmatics during and outside pollen season

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          Abstract

          Background

          Group 2 innate lymphoid cells (ILC2s) are a newly identified cell population with the potent capability to produce Th2-type cytokines in a non-antigen specific manner. Previous study demonstrated that enhanced circulating ILC2s in cat-allergic patient after experimental allergen challenge, whereas the effects of natural allergen exposure on peripheral ILC2s are still unclear. We therefore examined the variations in circulating ILC2s among asthmatic patients sensitized to different allergens in- and outside- pollen season.

          Methods

          10 patients sensitized to mugwort, 10 patients sensitized to house dust mites (HDM) and 12 healthy controls were recruited into this study. Blood samples were collected from the patients in- and outside- pollens season, 2–3 months apart. ILC2s (Lin-CD127+ CRTH2+) were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. The levels of IL-5 and IL-13 in supernatants of Lineage- and Lineage+ cells stimulated with IL-25 and/or IL-33 in the presence of IL-2 were measured using a Milliplex human cytokine array kit.

          Results

          An obvious seasonal increases in percentages of total and IL-13+ ILC2s were observed in patients with mugwort sensitization during natural pollen exposure, however, the percentages of peripheral ILC2s in HDM-allergic patients were not affected significantly. A positive correlation between FeNO and IL-13 +ILC2s was found in patients sensitized to mugwort. A mixture of IL-33 and IL-25 induced a significant production of IL-13 and IL-5 from Lineage cells of both mugwort-allergic and HDM-allergic asthmatics. Stimulation with IL-33 alone induced a significantly greater quantity of IL-13 by Lineage-cells from mugwort-allergic asthmatic compared with that from HDM-allergic asthmatics, whereas IL-25 induced a significantly greater amount of IL-5 by the Lineage-cells from mugwort-allergic asthmatic compared with that from HDM-allergic asthmatics.

          Conclusion

          Within pollen season the frequencies and function profiles of circulating ILC2s among asthmatic children are altered dynamically, which may be closely related to the sensitized type of allergens.

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          Most cited references20

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          Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161.

          Innate lymphoid cells (ILCs) are emerging as a family of effectors and regulators of innate immunity and tissue remodeling. Interleukin 22 (IL-22)- and IL-17-producing ILCs, which depend on the transcription factor RORγt, express CD127 (IL-7 receptor α-chain) and the natural killer cell marker CD161. Here we describe another lineage-negative CD127(+)CD161(+) ILC population found in humans that expressed the chemoattractant receptor CRTH2. These cells responded in vitro to IL-2 plus IL-25 and IL-33 by producing IL-13. CRTH2(+) ILCs were present in fetal and adult lung and gut. In fetal gut, these cells expressed IL-13 but not IL-17 or IL-22. There was enrichment for CRTH2(+) ILCs in nasal polyps of chronic rhinosinusitis, a typical type 2 inflammatory disease. Our data identify a unique type of human ILC that provides an innate source of T helper type 2 (T(H)2) cytokines.
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            Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33.

            Asthma in a mouse model spontaneously resolves after cessation of allergen exposure. We developed a mouse model in which asthma features persisted for 6 months after cessation of allergen exposure.
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              IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization.

              Allergen exposure at lung and gut mucosae can lead to aberrant T(H)2 immunity and allergic disease. The epithelium-associated cytokines thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 are suggested to be important for the initiation of these responses. We sought to investigate the contributions of TSLP, IL-25, and IL-33 in the development of allergic disease to the common allergens house dust mite (HDM) or peanut. Neutralizing antibodies or mice deficient in TSLP, IL-25, or IL-33 signaling were exposed to HDM intranasally or peanut intragastrically, and immune inflammatory and physiologic responses were evaluated. In vitro assays were performed to examine specific dendritic cell (DC) functions. We showed that experimental HDM-induced allergic asthma and food allergy and anaphylaxis to peanut were associated with TSLP production but developed independently of TSLP, likely because these allergens functionally mimicked TSLP inhibition of IL-12 production and induction of OX40 ligand (OX40L) on DCs. Blockade of OX40L significantly lessened allergic responses to HDM or peanut. Although IL-25 and IL-33 induced OX40L on DCs in vitro, only IL-33 signaling was necessary for intact allergic immunity, likely because of its superior ability to induce DC OX40L and expand innate lymphoid cells in vivo. These data identify a nonredundant, IL-33-driven mechanism initiating T(H)2 responses to the clinically relevant allergens HDM and peanut. Our findings, along with those in infectious and transgenic/surrogate allergen systems, favor a paradigm whereby multiple molecular pathways can initiate T(H)2 immunity, which has implications for the conceptualization and manipulation of these responses in health and disease. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Contributors
                bchmiaoqing@163.com
                wangyan@163.com
                liuyg@163.com
                renyixin@163.com
                guanhui@163.com
                lizhen@163.com
                xuwei22@163.com
                drxiangli@163.com
                Journal
                Allergy Asthma Clin Immunol
                Allergy Asthma Clin Immunol
                Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology
                BioMed Central (London )
                1710-1484
                1710-1492
                9 February 2018
                9 February 2018
                2018
                : 14
                : 6
                Affiliations
                Department of Allergy, Beijing Children’s Hospital, Capital Medical School, No. 56 Nanlishi Road, Xicheng District, Beijing, 100045 China
                Article
                229
                10.1186/s13223-018-0229-x
                5806282
                858ccdd2-c9c8-430f-ad08-73655f2c96c7
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 April 2017
                : 4 January 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004826, Natural Science Foundation of Beijing Municipality;
                Award ID: No. 7172074
                Award Recipient :
                Funded by: special research grant for non-profit public service
                Award ID: 2015SQ00136
                Award Recipient :
                Funded by: Foundation for Distinguished Young Scholars in Hospital under the Jurisdiction of Beijing Municipality of China
                Award ID: PX20181201
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Immunology
                asthma,group 2 innate lymphoid cells,mugwort,pollen,house dust mites
                Immunology
                asthma, group 2 innate lymphoid cells, mugwort, pollen, house dust mites

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