Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats
Spondyloarthritis (SpA) does not display the typical features of auto-immune disease. Despite the strong association with MHC class I, CD8+ T cells are not required for disease induction in the HLA-B27/Huβ2m transgenic rats. We used Lewis HLA-B27/Huβ2m transgenic rats [21-3 × 283-2]F1, HLA-B7/Huβ2m...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00920/full |
| _version_ | 1818304604586115072 |
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| author | Melissa N. van Tok Melissa N. van Tok Nimman Satumtira Martha Dorris Desirée Pots Desirée Pots Gleb Slobodin Marleen G. van de Sande Joel D. Taurog Dominique L. Baeten Dominique L. Baeten Leonie M. van Duivenvoorde Leonie M. van Duivenvoorde |
| author_facet | Melissa N. van Tok Melissa N. van Tok Nimman Satumtira Martha Dorris Desirée Pots Desirée Pots Gleb Slobodin Marleen G. van de Sande Joel D. Taurog Dominique L. Baeten Dominique L. Baeten Leonie M. van Duivenvoorde Leonie M. van Duivenvoorde |
| author_sort | Melissa N. van Tok |
| collection | DOAJ |
| description | Spondyloarthritis (SpA) does not display the typical features of auto-immune disease. Despite the strong association with MHC class I, CD8+ T cells are not required for disease induction in the HLA-B27/Huβ2m transgenic rats. We used Lewis HLA-B27/Huβ2m transgenic rats [21-3 × 283-2]F1, HLA-B7/Huβ2m transgenic rats [120-4 × 283-2]F1, and wild-type rats to test our hypothesis that SpA may be primarily driven by the innate immune response. In vitro, splenocytes were stimulated with heat-inactivated Mycobacterium tuberculosis and cytokine expression and production was measured. In vivo, male and female rats were immunized with 30, 60, or 90 µg of heat-inactivated M. tuberculosis and clinically monitored for spondylitis and arthritis development. After validation of the model, we tested whether prophylactic and therapeutic TNF targeting affected spondylitis and arthritis. In vitro stimulation with heat-inactivated M. tuberculosis strongly induced gene expression of pro-inflammatory cytokines such as TNF, IL-6, IL-1α, and IL-1β, in the HLA-B27 transgenic rats compared with controls. In vivo immunization induced an increased spondylitis and arthritis incidence and an accelerated and synchronized onset of spondylitis and arthritis in HLA-B27 transgenic males and females. Moreover, immunization overcame the protective effect of orchiectomy. Prophylactic TNF targeting resulted in delayed spondylitis and arthritis development and reduced arthritis severity, whereas therapeutic TNF blockade did not affect spondylitis and arthritis severity. Collectively, these data indicate that innate immune activation plays a role in the initiation of HLA-B27-associated disease and allowed to establish a useful in vivo model to study the cellular and molecular mechanisms of disease initiation and progression. |
| first_indexed | 2024-12-13T06:13:20Z |
| format | Article |
| id | doaj.art-7407f2e242be457d8bfd640de2dc8d2f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T06:13:20Z |
| publishDate | 2017-08-01 |
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| spelling | doaj.art-7407f2e242be457d8bfd640de2dc8d2f2022-12-21T23:57:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.00920284070Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic RatsMelissa N. van Tok0Melissa N. van Tok1Nimman Satumtira2Martha Dorris3Desirée Pots4Desirée Pots5Gleb Slobodin6Marleen G. van de Sande7Joel D. Taurog8Dominique L. Baeten9Dominique L. Baeten10Leonie M. van Duivenvoorde11Leonie M. van Duivenvoorde12Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsExperimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsRheumatic Diseases Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United StatesRheumatic Diseases Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United StatesClinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsExperimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsInternal Medicine, Bnai Zion Medical Center, Haifa, IsraelClinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsRheumatic Diseases Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United StatesClinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsExperimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsClinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsExperimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsSpondyloarthritis (SpA) does not display the typical features of auto-immune disease. Despite the strong association with MHC class I, CD8+ T cells are not required for disease induction in the HLA-B27/Huβ2m transgenic rats. We used Lewis HLA-B27/Huβ2m transgenic rats [21-3 × 283-2]F1, HLA-B7/Huβ2m transgenic rats [120-4 × 283-2]F1, and wild-type rats to test our hypothesis that SpA may be primarily driven by the innate immune response. In vitro, splenocytes were stimulated with heat-inactivated Mycobacterium tuberculosis and cytokine expression and production was measured. In vivo, male and female rats were immunized with 30, 60, or 90 µg of heat-inactivated M. tuberculosis and clinically monitored for spondylitis and arthritis development. After validation of the model, we tested whether prophylactic and therapeutic TNF targeting affected spondylitis and arthritis. In vitro stimulation with heat-inactivated M. tuberculosis strongly induced gene expression of pro-inflammatory cytokines such as TNF, IL-6, IL-1α, and IL-1β, in the HLA-B27 transgenic rats compared with controls. In vivo immunization induced an increased spondylitis and arthritis incidence and an accelerated and synchronized onset of spondylitis and arthritis in HLA-B27 transgenic males and females. Moreover, immunization overcame the protective effect of orchiectomy. Prophylactic TNF targeting resulted in delayed spondylitis and arthritis development and reduced arthritis severity, whereas therapeutic TNF blockade did not affect spondylitis and arthritis severity. Collectively, these data indicate that innate immune activation plays a role in the initiation of HLA-B27-associated disease and allowed to establish a useful in vivo model to study the cellular and molecular mechanisms of disease initiation and progression.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00920/fullspondyloarthritisinnate immunityHLA-B27 transgenic ratsinflammationbone formation |
| spellingShingle | Melissa N. van Tok Melissa N. van Tok Nimman Satumtira Martha Dorris Desirée Pots Desirée Pots Gleb Slobodin Marleen G. van de Sande Joel D. Taurog Dominique L. Baeten Dominique L. Baeten Leonie M. van Duivenvoorde Leonie M. van Duivenvoorde Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats Frontiers in Immunology spondyloarthritis innate immunity HLA-B27 transgenic rats inflammation bone formation |
| title | Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats |
| title_full | Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats |
| title_fullStr | Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats |
| title_full_unstemmed | Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats |
| title_short | Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats |
| title_sort | innate immune activation can trigger experimental spondyloarthritis in hla b27 huβ2m transgenic rats |
| topic | spondyloarthritis innate immunity HLA-B27 transgenic rats inflammation bone formation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00920/full |
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