{"created":"2023-06-19T07:18:54.994078+00:00","id":4541,"links":{},"metadata":{"_buckets":{"deposit":"03344225-69c8-4668-ad73-5339884600f8"},"_deposit":{"created_by":4,"id":"4541","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"4541"},"status":"published"},"_oai":{"id":"oai:az.repo.nii.ac.jp:00004541","sets":["370:15:391"]},"author_link":["19823","19822"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2016-09-30"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"麻布大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"32701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(獣医学)"}]},"item_10006_description_22":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Canine food allergy is an important allergic disease, which is caused by environmental and genetic factors. In humans, improvement of environmental hygiene is a factor of increasing allergic diseases, and it is called “hygiene hypothesis”. Recently, dogs have been living in the same environment as humans. Thus, the canine food allergy could be caused by the improvement of environmental hygiene as well as humans. On the other hand, genetic factors are associated with the development of canine food allergy because dogs of certain breeds frequently develop the canine food allergy. The pathology of canine food allergy is classified into IgE-mediated and non-IgE-mediated, which are intricately associated with the development of canine food allergy. Therefore, it is difficult to elucidate a mechanism of canine food allergy and establish efficient diagnoses and treatments. At present, food elimination therapy is used as common treatment for the canine food allergy. However, curative therapy for the canine food allergy has still not been established in veterinary medicine. If the curative therapy can be established, it will be a benefit for veterinary medicine. This study aimed to perform immunological analysis of canine food allergy and develop the curative therapy. \n First, pedigree dogs that have a high prevalence rate of the canine food allergy were examined. In case of single gene disorder, inheritance pattern in the pedigree was supposed to be autosomal dominant inheritance. All the dogs with canine food allergy exhibited non-IgE-mediated food allergy. Causative food allergens in three of the dogs with canine food allergy were determined by food provocation test. Two of the three dogs showed proliferation of causative food allergen-specific lymphocyte in lymphocyte proliferation test. The immunological mechanism of non-IgE-mediated food allergy is still not well understood. The dogs in this pedigree is useful as a model animal of non-IgE-mediated food allergy. \n Second, serological analysis was performed in dogs with IgE-mediated food allergy. Levels of specific IgE to crude egg white allergen which is common food allergen were measured. Eight of 82 dogs with cutaneous adverse food reaction showed IgE reactivity to crude egg white allergen. Moreover, IgE reactivity to four purified egg white allergens which are characterized in human studies was investigated in the eight dogs with IgE reactivity to crude egg white allergen. Six of the eight dogs showed IgE reactivity to ovomucoid and ovalbumin, and three of the eight dogs showed IgE reactivity to ovotransferrin. Additionally, the result indicated that ovotransferrin did not have a linear epitope. Thus, it can be considered that ovotransferrin is less important as food allergen. In this study, ovomucoid and ovalbumin appear to be major purified egg white allergens in dogs, and these results provided important data for study on IgE-mediated canine food allergy. \n Third, a basis examination of oral immunotherapy using allergen-expressing recombinant lactic acid bacteria was performed in a mouse model. To improve the therapeutic effect of oral immunotherapy as a candidate of curative therapy for food allergy, lactic acid bacteria were used as a transport carrier of allergens in this experiments. Ovalbumin-expressing Lactobacillus casei was orally administrated to mice, and anti-allergic effects of ovalbumin-expressing L. casei were examined. There were no differences in anaphylactic reaction and serum ovalbumin specific IgE levels between ovalbumin-expressing L. casei administration group and other groups. Thus, anti-allergic effect of ovalbumin-expressing L. casei was not confirmed. Further study is needed to develop allergen-expressing L. casei which could demonstrate sufficient anti-allergic effects. \n In conclusion, the immunological analysis of IgE-mediated and non-IgE-mediated canine food allergy were performed in this study. Oral immunotherapy using allergen-expressing lactic acid bacteria as a curative therapy for canine food allergy was examined. However, the anti-allergic effect of allergen-expressing recombinant lactic acid bacteria could not be confirmed. Further studies will be needed to identify the immune pathology of canine food allergy and to develop effective and curative therapy for canine food allergy. \n"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"イヌの食物アレルギーは重要なアレルギー疾患の一つである。食物アレルギーは環境要因と遺伝要因の両方が発症に関連していると考えられている。ヒトでは衛生環境の清浄化がアレルギー疾患の増加の一因だと考えられており、「衛生仮説」が提唱されている。近年、イヌもヒトと同じ環境で生活するようになっており、衛生環境の清浄化がイヌの食物アレルギーの発症にも影響を与えていると考えられる。また、食物アレルギーを発症しやすい犬種が報告されていることから、遺伝要因がイヌの食物アレルギーの発症に関わっていることも推測される。食物アレルギーの病態は大きくIgE依存性とIgE非依存性に分けられる。これらの病態が複雑に影響していることがアレルギーの機序の解明や診断方法・治療法の確立を困難にしている。現在、食物アレルギーの治療は原因食物の摂取を回避することが一般的に行われている。しかしながら、根本的な治療法は確立されていない。イヌの食物アレルギーを正確に診断し、有効な根治療法を適用できるようになれば、獣医療にとって大きなメリットがあると思われる。本研究の目的はイヌの食物アレルギーの免疫学的な解析を行い、それに対する治療法の研究開発を行うことである。\n　第1章では、高い頻度で食物アレルギーを発症する家系のイヌを調査した。本家系における食物アレルギーは常染色体優性遺伝が推定された。すべての食物アレルギーのイヌはIgE非依存性の食物アレルギーを示した。一部の食物アレルギーのイヌに対して食物負荷試験を実施し、食物負荷試験の前後で抗原特異的リンパ球の増殖能を検討したところ、3頭中2頭は原因食物アレルゲン特異的リンパ球の活性化が認められた。IgE非依存性食物アレルギーについての研究を行う上で、モデル動物として本研究の家系のイヌを用いることは意義があると考えられる。ヒトにおいてもIgE非依存性食物アレルギーの免疫学的機序は未だに不明な点が多く、今後、イヌの分野でも研究を進めて行く必要があると思われる。\n　第2章では、IgE依存性の食物アレルギーのイヌの血清学的解析を行った。一般的な食物アレルゲンである卵白の粗抗原に対するIgEを測定したところ、食物有害反応犬82頭中8頭（9.8%）が陽性を示した。ヒトにおいて調べられている4つの卵白精製抗原に対するIgE反応性を卵白粗抗原特異的IgE陽性を示した8頭のイヌで調べた結果、8頭中6頭（75.0%）はオボムコイドとオボアルブミンに陽性を示し、8頭中3頭（37.5%）はオボトランスフェリンに陽性を示した。本研究において、ヒトと同様にオボムコイドとオボアルブミンがイヌの主要な卵白精製抗原だということが示唆された。本研究におけるイヌの卵アレルギーはヒトのモデルとしても有用であることが判った。\n　第3章では、マウスを用いてアレルゲン発現組換え乳酸菌の経口免疫療法の基礎的検討を行った。食物アレルギーの根治療法の候補として研究されている経口免疫療法のさらなる治療効果向上を目的として、プロバイオティクスとして注目されている乳酸菌をアレルゲンの輸送担体として用いて実験を行った。卵白精製抗原であるオボアルブミンを発現したLactobacillus caseiをマウスに経口投与し、オボアルブミン発現L. caseiの抗アレルギー効果を検討した。オボアルブミン発現L. caseiを投与した群のアナフィラキシー反応や血清中IgEの結果は他の群と比較して違いがなく、抗アレルギー効果は認められなかった。今後、経口免疫寛容誘導に必要な抗原量の検討を行い、それらの情報を基にアレルゲン発現L. caseiの改良を行う必要があると考えられる。\n　本研究では、イヌのIgE依存性ならびに非依存性の食物アレルギーの免疫学的な解析を行った。さらにイヌの食物アレルギーの根治療法として、アレルゲン発現組換え乳酸菌を用いた経口免疫療法の基礎的な研究を行った。イヌの卵アレルギーにおいて卵の各精製アレルゲンに対するIgE抗体の反応性を検討して、ヒトの卵アレルギーにおけるIgE反応性とよく似ていることを明らかにした。本研究のイヌの卵アレルギーはヒトのモデルとしても有用であることが判った。また、本研究における遺伝的に非依存性食物アレルギーを発症するイヌも食物アレルギーを研究する上で有用なモデルとなると思われる。アレルゲン発現組換え乳酸菌を用いた経口免疫療法については今後さらなる研究を行い、有効な根治療法の開発をしていく予定である。\n"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第147号"}]},"item_10006_textarea_23":{"attribute_name":"Rights","attribute_value_mlt":[{"subitem_textarea_value":"本論文の一部は以下のとおり公表されている。(Part of this dissertation has been published as follows.) \nShimakura, H., Uchiyama, J., Saito, T., Miyaji, K., Fujimura, M., Masuda, K., Okamoto, N., DeBoer, DJ., Sakaguchi, M.: IgE reactivity to hen egg white allergens in dogs with cutaneous adverse food reactions. Veterinary immunology and immunopathology, 177: 52-57, 2016. http://dx.doi.org/10.1016/j.vetimm.2016.06.003."}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"島倉, 秀勝"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Shimakura, Hidekatsu","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-10-19"}],"displaytype":"detail","filename":"diss_dv_kou0147.pdf","filesize":[{"value":"6.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"diss_dv_kou0147","url":"https://az.repo.nii.ac.jp/record/4541/files/diss_dv_kou0147.pdf"},"version_id":"7ca52240-0913-4981-9663-61bdb71e7b40"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-10-19"}],"displaytype":"detail","filename":"diss_dv_kou0147_jab&rev.pdf","filesize":[{"value":"152.5 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"diss_dv_kou0147_jab&rev.pdf","url":"https://az.repo.nii.ac.jp/record/4541/files/diss_dv_kou0147_jab&rev.pdf"},"version_id":"0e3554ef-b914-4ba3-bbba-fe46962f7c70"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis"}]},"item_title":"イヌの食物アレルギーにおける免疫学的解析および免疫療法に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"イヌの食物アレルギーにおける免疫学的解析および免疫療法に関する研究"},{"subitem_title":"Study on immunological analysis and immunotherapy for canine food allergy.","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"4","path":["391"],"pubdate":{"attribute_name":"公開日","attribute_value":"2016-10-19"},"publish_date":"2016-10-19","publish_status":"0","recid":"4541","relation_version_is_last":true,"title":["イヌの食物アレルギーにおける免疫学的解析および免疫療法に関する研究"],"weko_creator_id":"4","weko_shared_id":4},"updated":"2023-06-19T08:03:39.490751+00:00"}