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      Allergen immunotherapy: past, present and future

      review-article
      ,
      Nature Reviews. Immunology
      Nature Publishing Group UK
      Applied immunology, Translational research

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          Abstract

          Allergen immunotherapy is a form of therapeutic vaccination for established IgE-mediated hypersensitivity to common allergen sources such as pollens, house dust mites and the venom of stinging insects. The classical protocol, introduced in 1911, involves repeated subcutaneous injection of increasing amounts of allergen extract, followed by maintenance injections over a period of 3 years, achieving a form of allergen-specific tolerance that provides clinical benefit for years after its discontinuation. More recently, administration through the sublingual route has emerged as an effective, safe alternative. Oral immunotherapy for peanut allergy induces effective ‘desensitization’ but not long-term tolerance. Research and clinical trials over the past few decades have elucidated the mechanisms underlying immunotherapy-induced tolerance, involving a reduction of allergen-specific T helper 2 (T H2) cells, an induction of regulatory T and B cells, and production of IgG and IgA ‘blocking’ antibodies. To better harness these mechanisms, novel strategies are being explored to achieve safer, effective, more convenient regimens and more durable long-term tolerance; these include alternative routes for current immunotherapy approaches, novel adjuvants, use of recombinant allergens (including hypoallergenic variants) and combination of allergens with immune modifiers or monoclonal antibodies targeting the T H2 cell pathway.

          Abstract

          Durham and Shamji review the history and future of allergen immunotherapy for established IgE-mediated hypersensitivity to common allergens. They describe the mechanisms of immunotherapy-induced tolerance and the new strategies being explored to achieve safer, more effective, long-term tolerance.

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          Most cited references164

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          Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen).

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            A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism

            Foxp3+ regulatory T (T reg) cells play a key role in controlling immune pathological re actions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Foxp3+ T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-β can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. Here, we show that after antigen activation in the intestine, naive T cells acquire expression of Foxp3. Moreover, we identify a population of CD103+ mesenteric lymph node dendritic cells (DCs) that induce the devel opment of Foxp3+ T reg cells. Importantly, promotion of T reg cell responses by CD103+ DCs is dependent on TGF-β and the dietary metabolite, retinoic acid (RA). These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine.
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              Prevalence and rate of diagnosis of allergic rhinitis in Europe.

              To measure the prevalence of allergic rhinitis among European adults and the proportion of undiagnosed subjects, a two-step, cross-sectional, population-based survey in Belgium, France, Germany, Italy, Spain, and the UK was undertaken. Step one of the study involved screening for allergic rhinitis by telephone interview, based on history of symptoms and/or self-awareness of the condition. Step two undertook confirmation of allergic rhinitis in a subset of the subjects screened positive; this was performed by a clinical diagnosis conducted in three to five clinical centres per country, including specific immunoglobulin E tests and a disease-specific questionnaire. A total of 9,646 telephone interviews were conducted between February and April 2001. Self-awareness of allergic rhinitis was reported by 19% of the subjects. Physician-based diagnosis of allergic rhinitis was reported by 13% of the subjects. In step two, 725 clinical assessments were conducted between May and August 2001. A total of 411 of patients, who underwent step two, had investigator-confirmed allergic rhinitis. Among patients with investigator-confirmed allergic rhinitis, 45% had not reported a previous diagnosis by a physician. Prevalence of subjects with clinically confirmable allergic rhinitis estimated by combining step one and step two data ranged from 17% in Italy to 29% in Belgium with an overall value of 23%. This large-scale study confirms that allergic rhinitis has a high prevalence in western Europe and is frequently undiagnosed.
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                Author and article information

                Contributors
                s.durham@imperial.ac.uk
                m.shamji99@imperial.ac.uk
                Journal
                Nat Rev Immunol
                Nat Rev Immunol
                Nature Reviews. Immunology
                Nature Publishing Group UK (London )
                1474-1733
                1474-1741
                17 October 2022
                : 1-12
                Affiliations
                GRID grid.7445.2, ISNI 0000 0001 2113 8111, Allergy and Clinical Immunology, National Heart and Lung Institute, , Imperial College London, ; London, UK
                Author information
                http://orcid.org/0000-0001-5264-6207
                Article
                786
                10.1038/s41577-022-00786-1
                9575636
                36253555
                1b31fcc1-c75d-40da-b3af-148205332756
                © Springer Nature Limited 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 8 September 2022
                Categories
                Perspective

                applied immunology,translational research
                applied immunology, translational research

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