دورية أكاديمية
أعرض في EDS

Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association.

التفاصيل البيبلوغرافية
العنوان: Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association.
المؤلفون: Romero-Castillo L; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Li T; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Do NN; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Sareila O; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.; Medical Inflammation Research, MediCity Research Laboratory, University of Turku, Turku, FI-20520, Finland., Xu B; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Hennings V; Department of Pediatrics, Institute of Clinical Sciences and Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden., Xu Z; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Svensson C; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Oliveira-Coelho A; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Sener Z; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Urbonaviciute V; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden., Ekwall O; Department of Pediatrics, Institute of Clinical Sciences and Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden., Burkhardt H; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.; Division of Rheumatology, University Hospital Frankfurt, Goethe University, 60590, Frankfurt am Main, Germany., Holmdahl R; Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.; Medical Inflammation Research, MediCity Research Laboratory, University of Turku, Turku, FI-20520, Finland.
المصدر: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Jun; Vol. 11 (23), pp. e2401513. Date of Electronic Publication: 2024 Apr 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Weinheim : WILEY-VCH, [2014]-
مواضيع طبية MeSH: Arthritis, Rheumatoid*/genetics , Arthritis, Rheumatoid*/immunology , Antigens, Differentiation, B-Lymphocyte*/genetics , Antigens, Differentiation, B-Lymphocyte*/immunology , Disease Models, Animal* , Mice, Inbred C57BL* , Mice, Transgenic* , Gene Knock-In Techniques*/methods , Histocompatibility Antigens Class II*/genetics , Histocompatibility Antigens Class II*/immunology , Alleles*, Animals ; Mice ; Humans ; Arthritis, Experimental/genetics ; Arthritis, Experimental/immunology ; HLA-DRB1 Chains/genetics ; HLA-DRB1 Chains/immunology ; Collagen Type II/genetics ; Collagen Type II/immunology
مستخلص: Transgenic mice expressing human major histocompatibility complex class II (MHCII) risk alleles are widely used in autoimmune disease research, but limitations arise due to non-physiologic expression. To address this, physiologically relevant mouse models are established via knock-in technology to explore the role of MHCII in diseases like rheumatoid arthritis. The gene sequences encoding the ectodomains are replaced with the human DRB1*04:01 and 04:02 alleles, DRA, and CD74 (invariant chain) in C57BL/6N mice. The collagen type II (Col2a1) gene is modified to mimic human COL2. Importantly, DRB1*04:01 knock-in mice display physiologic expression of human MHCII also on thymic epithelial cells, in contrast to DRB1*04:01 transgenic mice. Humanization of the invariant chain enhances MHCII expression on thymic epithelial cells, increases mature B cell numbers in spleen, and improves antigen presentation. To validate its functionality, the collagen-induced arthritis (CIA) model is used, where DRB1*04:01 expression led to a higher susceptibility to arthritis, as compared with mice expressing DRB1*04:02. In addition, the humanized T cell epitope on COL2 allows autoreactive T cell-mediated arthritis development. In conclusion, the humanized knock-in mouse faithfully expresses MHCII, confirming the DRB1*04:01 alleles role in rheumatoid arthritis and being also useful for studying MHCII-associated diseases.
(© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
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معلومات مُعتمدة: Swedish Association against Rheumatism; Academy of Finland; 2019-01209 Swedish Medical Research Council; 2022-00781 Swedish Medical Research Council; Swedish State under the agreement between the Swedish government and the county councils; ALFGBG-965795 ALF-agreement; Spanish Ministry of Universities and NextGeneration EU; 2019-0059 Knut och Alice Wallenbergs Stiftelse; LF-OC-22-001023 Leo Foundation; 222350Pj01H Cancerfonden
فهرسة مساهمة: Keywords: CIA; DTH; MHC class II; autoimmune diseases; humanized mice; rheumatoid arthritis
المشرفين على المادة: 0 (invariant chain)
0 (Antigens, Differentiation, B-Lymphocyte)
0 (Histocompatibility Antigens Class II)
0 (HLA-DRB1 Chains)
0 (Collagen Type II)
تواريخ الأحداث: Date Created: 20240411 Date Completed: 20240619 Latest Revision: 20240709
رمز التحديث: 20240709
مُعرف محوري في PubMed: PMC11187888
DOI: 10.1002/advs.202401513
PMID: 38602454
قاعدة البيانات: MEDLINE
الوصف
تدمد:2198-3844
DOI:10.1002/advs.202401513