{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T04:20:53Z","timestamp":1773116453221,"version":"3.50.1"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for JSPS KAKENHI","award":["15K08626, 19K09901, 20H00555"],"award-info":[{"award-number":["15K08626, 19K09901, 20H00555"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Owing to the successful application of sublingual immunotherapy (SLIT), allergen immunotherapy (AIT) has become one of the leading treatments for allergic diseases. Similar to the case with other AITs, such as subcutaneous and oral immunotherapies, not only the alleviation of allergic symptoms, but also the curing of the diseases can be expected in patients undergoing SLIT. However, how and why such strong efficacy is obtained by SLIT, in which allergens are simply administered under the tongue, is not clearly known. Various potential mechanisms, including the induction of blocking antibodies, T cell tolerance, regulatory B and T cells, CD103-CD11b+ classical dendritic cells, and CD206+ macrophages, and the reduction of innate lymphoid cells, mast cells, and basophils, have been suggested. Recently, through a comparative analysis between high- and non-responder patients of SLIT, we have successfully proposed several novel mechanisms. Here, we introduce our recent findings and summarize the current understanding of the mechanisms underlying the strong efficacy of SLIT.<\/jats:p>","DOI":"10.3390\/pathogens10020147","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T05:44:42Z","timestamp":1612244682000},"page":"147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sublingual Immunotherapy: How Sublingual Allergen Administration Heals Allergic Diseases; Current Perspective about the Mode of Action"],"prefix":"10.3390","volume":"10","author":[{"given":"Minoru","family":"Gotoh","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Nippon Medical School, Tokyo 113-8603, Japan"},{"name":"Laboratory of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1211-0410","authenticated-orcid":false,"given":"Osamu","family":"Kaminuma","sequence":"additional","affiliation":[{"name":"Laboratory of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"},{"name":"Department of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.2165\/11640800-000000000-00000","article-title":"Sublingual vs oral immunotherapy for food allergy: Identifying the right approach","volume":"72","author":"Narisety","year":"2012","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.4049\/jimmunol.97.6.840","article-title":"Physicochemical properties of reaginic antibody. V. Correlation of reaginic activity wth gamma-E-globulin antibody","volume":"97","author":"Ishizaka","year":"1966","journal-title":"J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13601-017-0170-y","article-title":"The efficacy of oral and subcutaneous antigen-specific immunotherapy in murine cow\u2019s milk- and peanut allergy models","volume":"7","author":"Vonk","year":"2017","journal-title":"Clin. Transl. Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1172\/JCI107204","article-title":"IgE antibody measurements in ragweed hay fever. Relationship to clinical severity and the results of immunotherapy","volume":"52","author":"Lichtenstein","year":"1973","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1046\/j.1365-2222.1998.00295.x","article-title":"Activation of B-lymphocytes during pollen season. Effect of immunotherapy","volume":"28","author":"Heinrich","year":"1998","journal-title":"Clin. Exp. Allergy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1046\/j.1365-2222.2003.01699.x","article-title":"Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: Reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies","volume":"33","author":"Mothes","year":"2003","journal-title":"Clin. Exp. Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1034\/j.1398-9995.1999.00916.x","article-title":"Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: A double-blind, placebo-controlled study","volume":"54","author":"Bousquet","year":"1999","journal-title":"Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0091-6749(99)70388-X","article-title":"Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis","volume":"104","author":"Ranno","year":"1999","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1034\/j.1398-9995.2000.00495.x","article-title":"Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: A double-blind, placebo-controlled study","volume":"55","author":"Pajno","year":"2000","journal-title":"Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.jaci.2008.01.072","article-title":"Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity","volume":"121","author":"Francis","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.4049\/jimmunol.163.5.2944","article-title":"Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation","volume":"163","author":"Wikborg","year":"1999","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jaci.2010.12.1080","article-title":"Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies","volume":"127","author":"James","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0022-1759(93)90111-J","article-title":"Purification of human IgG4 subclass with allergen-specific blocking activity","volume":"165","author":"Lambin","year":"1993","journal-title":"J. Immunol. Methods"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/all.12607","article-title":"Inhibition of allergen-dependent IgE activity by antibodies of the same specificity but different class","volume":"70","author":"Dodev","year":"2015","journal-title":"Allergy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/all.14073","article-title":"Induction of IgG(2) and IgG(4) B-cell memory following sublingual immunotherapy for ryegrass pollen allergy","volume":"75","author":"Heeringa","year":"2020","journal-title":"Allergy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jaci.2013.09.043","article-title":"Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation","volume":"133","author":"Ramos","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1159\/000083956","article-title":"Impact of sublingual immunotherapy on specific antibody levels in asthmatic children allergic to house dust mites","volume":"136","author":"Bahceciler","year":"2005","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1046\/j.0954-7894.2002.01327.x","article-title":"Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: A randomized controlled trial","volume":"32","author":"Lima","year":"2002","journal-title":"Clin. Exp. Allergy"},{"key":"ref_19","first-page":"25","article-title":"Sublingual immunotherapy in Parietaria pollen-induced rhinitis: A double-blind study","volume":"5","author":"Troise","year":"1995","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1398-9995.1998.tb04086.x","article-title":"Clinical efficacy of sublingual-swallow immunotherapy: A double-blind, placebo-controlled trial of a standardized five-grass-pollen extract in rhinitis","volume":"53","author":"Clavel","year":"1998","journal-title":"Allergy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1111\/cea.13169","article-title":"Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma","volume":"48","author":"Hesse","year":"2018","journal-title":"Clin. Exp. Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.4049\/jimmunol.0903909","article-title":"Suppression of Th2-driven airway inflammation by allergen immunotherapy is independent of B cell and Ig responses in mice","volume":"185","author":"Shirinbak","year":"2010","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ebiom.2016.08.022","article-title":"Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy","volume":"11","author":"Zieglmayer","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.jaci.2018.10.061","article-title":"Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy","volume":"143","author":"Boonpiyathad","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jaci.2019.11.046","article-title":"Allergen-specific IgG(+) memory B cells are temporally linked to IgE memory responses","volume":"146","author":"Hoof","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1111\/all.12490","article-title":"Regulatory functions of B cells in allergic diseases","volume":"69","author":"Braza","year":"2014","journal-title":"Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.jaci.2016.03.017","article-title":"Regulatory B cells and T follicular helper cells are reduced in allergic rhinitis","volume":"138","author":"Kim","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.jaci.2014.07.041","article-title":"IL-10-overexpressing B cells regulate innate and adaptive immune responses","volume":"135","author":"Stanic","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.clim.2015.02.016","article-title":"Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma","volume":"158","author":"Kamekura","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/all.12966","article-title":"High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers","volume":"72","author":"Boonpiyathad","year":"2017","journal-title":"Allergy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.jaci.2010.01.018","article-title":"Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model","volume":"125","author":"Amu","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/j.1365-2222.1997.tb01252.x","article-title":"Immunological changes during specific immunotherapy of grass pollen allergy: Reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phl p 1, a major grass pollen allergen","volume":"27","author":"Ebner","year":"1997","journal-title":"Clin. Exp. Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.4049\/jimmunol.154.8.4187","article-title":"Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures","volume":"154","author":"Jutel","year":"1995","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1084\/jem.178.6.2123","article-title":"Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals","volume":"178","author":"Secrist","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.jaci.2014.05.033","article-title":"Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy","volume":"134","author":"Schulten","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1007\/s10753-015-0204-3","article-title":"Cytokine Responses to Specific Immunotherapy in House Dust Mite-Induced Allergic Rhinitis Patients","volume":"38","author":"Li","year":"2015","journal-title":"Inflammation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1365-2222.1997.tb00671.x","article-title":"House dust mite immunotherapy results in a decrease in Der p 2-specific IFN-gamma and IL-4 expression by circulating T lymphocytes","volume":"27","author":"Byron","year":"1997","journal-title":"Clin. Exp. Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/cea.12653","article-title":"Distinct modulation of allergic T cell responses by subcutaneous vs. sublingual allergen-specific immunotherapy","volume":"46","author":"Schulten","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/all.13779","article-title":"Sublingual immunotherapy with recombinant Mal d 1 downregulates the allergen-specific Th2 response","volume":"74","author":"Kinaciyan","year":"2019","journal-title":"Allergy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S1081-1206(10)60597-2","article-title":"Effect of sublingual immunotherapy with grass monomeric allergoid on allergen-specific T-cell proliferation and interleukin 10 production","volume":"100","author":"Burastero","year":"2008","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.jaci.2007.06.013","article-title":"Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation","volume":"120","author":"Bohle","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nri2262","article-title":"Treatment strategies for allergy and asthma","volume":"8","author":"Holgate","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.iy.12.040194.001455","article-title":"Immunological aspects of allergic asthma","volume":"12","author":"Bochner","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1067\/mai.2003.1570","article-title":"Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy","volume":"111","author":"Francis","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104251","DOI":"10.1016\/j.cellimm.2020.104251","article-title":"Role of orally induced regulatory T cells in immunotherapy and tolerance","volume":"359","author":"Bertolini","year":"2020","journal-title":"Cell. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sharif, H., Acharya, S., Dhondalay, G.K.R., Varricchi, G., Krasner-Macleod, S., Laisuan, W., Switzer, A., Lenormand, M., Kashe, E., and Parkin, R.V. (2020). Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy. J. Allergy Clin. Immunol.","DOI":"10.1016\/j.jaci.2020.10.035"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion","volume":"34","author":"Morita","year":"2011","journal-title":"Immunity"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S1081-1206(10)61186-6","article-title":"Induction of interleukin 10 by sublingual immunotherapy for house dust mites: A preliminary report","volume":"95","author":"Ciprandi","year":"2005","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"398","DOI":"10.4049\/immunohorizons.1800076","article-title":"IL-10 Indirectly Downregulates IL-4-Induced IgE Production by Human B Cells","volume":"2","author":"Lin","year":"2018","journal-title":"ImmunoHorizons"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.jaci.2018.06.041","article-title":"Role of IL-35 in sublingual allergen immunotherapy","volume":"143","author":"Shamji","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/pai.13061","article-title":"Allergen-specific immunotherapy enhances CD8(+) CD25(+) CD137(+) regulatory T cells and decreases nasal nitric oxide","volume":"30","author":"Tsai","year":"2019","journal-title":"Pediatric Allergy Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhang, R., Miao, J., and Zhu, P. (2020). Regulatory T cell heterogeneity and therapy in autoimmune diseases. Autoimmun. Rev., 102715.","DOI":"10.1016\/j.autrev.2020.102715"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1046\/j.1365-2222.2001.00999.x","article-title":"Pharmacokinetics of an allergen and a monomeric allergoid for oromucosal immunotherapy in allergic volunteers","volume":"31","author":"Bagnasco","year":"2001","journal-title":"Clin. Exp. Allergy"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/cea.12329","article-title":"Transportation of sublingual antigens across sublingual ductal epithelial cells to the ductal antigen-presenting cells in mice","volume":"45","author":"Nagai","year":"2015","journal-title":"Clin. Exp. Allergy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.job.2019.02.001","article-title":"Mechanisms underlying the induction of regulatory T cells by sublingual immunotherapy","volume":"61","author":"Tanaka","year":"2019","journal-title":"J. Oral Biosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/mi.2016.46","article-title":"Oral CD103(-)CD11b(+) classical dendritic cells present sublingual antigen and induce Foxp3(+) regulatory T cells in draining lymph nodes","volume":"10","author":"Tanaka","year":"2017","journal-title":"Mucosal. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"733","DOI":"10.4049\/jimmunol.1002701","article-title":"Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell\/APC ratio, source of mouse strain, and regional localization","volume":"187","author":"Denning","year":"2011","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/imm.12747","article-title":"Mesenteric lymph node CD11b(-) CD103(+) PD-L1(High) dendritic cells highly induce regulatory T cells","volume":"152","author":"Shiokawa","year":"2017","journal-title":"Immunology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/intimm\/dxaa014","article-title":"Tolerogenic properties of CD206+ macrophages appeared in the sublingual mucosa after repeated antigen-painting","volume":"32","author":"Yang","year":"2020","journal-title":"Int. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2217\/imt.12.157","article-title":"Sublingual immunotherapy for allergic rhinitis and conjunctivitis","volume":"5","author":"Passalacqua","year":"2013","journal-title":"Immunotherapy"},{"key":"ref_61","first-page":"34","article-title":"Allergen immunotherapy as a drug: The new deal of grass allergen tablets from clinical trials to current practice","volume":"45","author":"Manzotti","year":"2013","journal-title":"Eur. Ann. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/intimm\/dxx034","article-title":"Identification of biomarker sets for predicting the efficacy of sublingual immunotherapy against pollen-induced allergic rhinitis","volume":"29","author":"Gotoh","year":"2017","journal-title":"Int. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3389\/fimmu.2019.00175","article-title":"Current Strategies to Inhibit High Affinity Fc\u03b5RI-Mediated Signaling for the Treatment of Allergic Disease","volume":"10","author":"Gomez","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2014.07.004","article-title":"Basophils have emerged as a key player in immunity","volume":"31C","author":"Karasuyama","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.alit.2019.03.007","article-title":"Thrombospondin 1-mediated suppression of mast cell degranulation is involved in the efficacy of sublingual immunotherapy","volume":"68s","author":"Kaminuma","year":"2019","journal-title":"Allergol. Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1111\/j.1398-9995.2006.01147.x","article-title":"Mechanism for acute oral desensitization to antibiotics","volume":"61","author":"Woo","year":"2006","journal-title":"Allergy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12858","DOI":"10.1074\/jbc.M114.623421","article-title":"Thrombospondin-1 (TSP1)-producing B cells restore antigen (Ag)-specific immune tolerance in an allergic environment","volume":"290","author":"Yang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","article-title":"Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins","volume":"136","author":"Mosmann","year":"1986","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Miura, K., Inoue, K., Ogura, A., and Kaminuma, O. (2020). Role of CD4(+) T Cells in Allergic Airway Diseases: Learning from Murine Models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207480"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1016\/j.jaci.2019.01.047","article-title":"Gene expression signatures of circulating human type 1, 2, and 3 innate lymphoid cells","volume":"143","author":"Li","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.clim.2017.09.008","article-title":"Increased innate type 2 immune response in house dust mite-allergic patients with allergic rhinitis","volume":"183","author":"Zhong","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jaci.2014.06.024","article-title":"Enhanced innate type 2 immune response in peripheral blood from patients with asthma","volume":"134","author":"Bartemes","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.jaci.2014.07.029","article-title":"Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy","volume":"134","author":"Steveling","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.iac.2019.09.009","article-title":"Mechanisms of Subcutaneous and Sublingual Aeroallergen Immunotherapy: What Is New?","volume":"40","author":"Sokolowska","year":"2020","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"662","DOI":"10.4168\/aair.2018.10.6.662","article-title":"Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy","volume":"10","author":"Mitthamsiri","year":"2018","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.alit.2018.02.003","article-title":"Involvement of taste receptors in the effectiveness of sublingual immunotherapy","volume":"67","author":"Gotoh","year":"2018","journal-title":"Allergol. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.bbi.2009.02.016","article-title":"Immune cells of the human peripheral taste system: Dominant dendritic cells and CD4 T cells","volume":"23","author":"Feng","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"562","DOI":"10.4168\/aair.2018.10.5.562","article-title":"Microarray-Based Multivariate Analysis of the Effectiveness of Sublingual Immunotherapy for Cedar Pollinosis","volume":"10","author":"Gotoh","year":"2018","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1159\/000126060","article-title":"Induction of apoptosis in human basophils by anti-Fas antibody treatment in vitro","volume":"146","author":"Matsumoto","year":"2008","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/iid3.314","article-title":"Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy","volume":"8","author":"Otsuka","year":"2020","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/j.1600-0625.2006.00477.x","article-title":"The 21st century renaissance of the basophil? Current insights into its role in allergic responses and innate immunity","volume":"15","author":"Falcone","year":"2006","journal-title":"Exp. Dermatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/pbi.12007","article-title":"Oral immunotherapy with transgenic rice seed containing destructed Japanese cedar pollen allergens, Cry j 1 and Cry j 2, against Japanese cedar pollinosis","volume":"11","author":"Wakasa","year":"2013","journal-title":"Plant Biotechnol. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000381059","article-title":"Efficacy and safety of sublingual immunotherapy for two seasons in patients with Japanese cedar pollinosis","volume":"166","author":"Okamoto","year":"2015","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.jaip.2018.11.044","article-title":"Long-Term Efficacy and Dose-Finding Trial of Japanese Cedar Pollen Sublingual Immunotherapy Tablet","volume":"7","author":"Gotoh","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.alit.2019.07.007","article-title":"Safety profile and immunological response of dual sublingual immunotherapy with house dust mite tablet and Japanese cedar pollen tablet","volume":"69","author":"Gotoh","year":"2020","journal-title":"Allergol. Int."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/2\/147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:18:36Z","timestamp":1760159916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/2\/147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":85,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["pathogens10020147"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10020147","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,2]]}}}