CD4+ T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus

Hoentjen, Frank; Tonkonogy, Susan L.; Qian, Bi-Feng; Liu, Bo; Dieleman, Levinus A.; Sartor, R. Balfour

doi:10.1002/ibd.20040

Cited by 24 publications

(14 citation statements)

References 37 publications

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“…It was recently reported that all of the disease features develop unimpeded in B27/hß 2 m transgenic rats lacking a functional CD8a gene, despite profoundly impaired CTL responses 83 . Similar results have been observed in cell transfer and depletion experiments 84,85,86 . To the extent that the rat model mirrors the role of B27 in human SpA, these results challenge the hypothesis that CD8+ T cell recognition of B27 is central to disease pathogenesis.…”

Section: Hla-b27 Transgenic Ratssupporting

confidence: 91%

The Role of HLA-B27 in Spondyloarthritis

Taurog¹

2010

J Rheumatol

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This article summarizes the proceedings of a one-day international workshop held in July 2009 on the role of HLA-B27 in the pathogenesis of ankylosing spondylitis (AS) and related disorders. HLA-B27 is found in about 90% of patients with AS, with an odds ratio of about 100, but the mechanism underlying this association is not known. There are currently 3 major mechanistic hypotheses for this association: (1) T cell recognition of one or more B27 presented peptides; (2) B27 heavy-chain misfolding that induces an unfolded protein response; and (3) innate immune recognition of cell-surface expressed B27 heavy-chain dimers. None of these hypotheses accounts for the tissue specificity of the inflammation characteristic of AS. These hypotheses were discussed in the context of known epidemiologic, biochemical, structural, and immunologic differences among HLA-B27 subtypes; data from the HLA-B27 transgenic rat model of spondyloarthritis; the growing list of other genes that have been found to be associated with AS; and other data on the pathogenesis of spondyloarthritis. Proposed directions for future research include expanded efforts to define similarities and differences among the B27 subtypes; further development of animal models; identifying the interactions of B27 with the products of other genes associated with AS; and continued investigation into the pathogenesis of spondyloarthritis.

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Section: Hla-b27 Transgenic Ratssupporting

confidence: 91%

The Role of HLA-B27 in Spondyloarthritis

Taurog¹

2010

J Rheumatol

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“…Conflicting data exist on the role of B. vulgatus in the pathogenesis of IBD. Germ-free rats transgenically expressing HLA-B27, a human MHC class I allele linked to spondyloarthritis-associated IBD (Brakenhoff et al, 2010), developed T-cell dependent colitis when colonized with B. vulgatus but not with various other bacteria including E. coli (Hoentjen et al, 2007; Rath et al, 1999). Interestingly, E. coli but not Bacteroides species were enriched in the intestines of conventionally raised, spontaneously colitic transgenic rats (Onderdonk et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Commensal Bacteroides Species Induce Colitis in Host-Genotype-Specific Fashion in a Mouse Model of Inflammatory Bowel Disease

Bloom

Bijanki

Nava

et al. 2011

Cell Host & Microbe

438

331

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SUMMARY The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here we fulfilled Koch’s postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively re-isolated them in culture. The bacteria colonized IBD-susceptible and non-susceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD.

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“…If these HLA-B27 transgenic animals were kept in a germ-free environment, they did not develop arthritis. Recolonization of the gut with Bacteroides vulgatus resulted in inflammatory changes [50,51]. However, introducing Lactobacillus and fusiform bacteria to the gut of germ-free animals had shown no such effect.…”

Section: Contribution To Diseasementioning

confidence: 99%

Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases

2018

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Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.

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CD4+ T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus

Abstract: These results implicate CD4(+) T cells in the development of colitis in HLA-B27 TG rats monoassociated with the nonpathogenic bacterial strain B. vulgatus.

Cited by 24 publications

References 37 publications

The Role of HLA-B27 in Spondyloarthritis

The Role of HLA-B27 in Spondyloarthritis

Commensal Bacteroides Species Induce Colitis in Host-Genotype-Specific Fashion in a Mouse Model of Inflammatory Bowel Disease

Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases

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