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Human MHC Class II ...
Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association
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Romero-Castillo, Laura (author)
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Li, Taotao (author)
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Do, Nhu Nguyen (author)
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- Sareila, Outi (author)
- Karolinska Institutet
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Xu, Bingze (author)
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- Hennings, Viktoria (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Clinical Sciences, Department of Pediatrics
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- Xu, Zhongwei (author)
- Karolinska Institutet
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Svensson, Carolin (author)
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- Oliveira-Coelho, Ana (author)
- Karolinska Institutet
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Sener, Zeynep (author)
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- Urbonaviciute, Vilma (author)
- Karolinska Institutet
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- Ekwall, Olov, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Clinical Sciences, Department of Pediatrics
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Burkhardt, Harald (author)
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- Holmdahl, Rikard (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Advanced Science. - 2198-3844.
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- autoimmune diseases
- CIA
- DTH
- humanized mice
- MHC class II
- rheumatoid arthritis
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Romero-Castillo, ...
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Li, Taotao
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Do, Nhu Nguyen
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Sareila, Outi
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Xu, Bingze
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Hennings, Viktor ...
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show more...
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Xu, Zhongwei
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Svensson, Caroli ...
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Oliveira-Coelho, ...
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Sener, Zeynep
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Urbonaviciute, V ...
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Ekwall, Olov, 19 ...
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Burkhardt, Haral ...
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Holmdahl, Rikard
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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Advanced Science
- By the university
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University of Gothenburg
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Karolinska Institutet