Balb/c FasKO mice develop allergic blepharitis associated with hyper-production of IgE

Ayumi Fukuoka,Kenji Nakanishi,Shin Yonehara,Hirotaka Kazama,Shizue Yumikura-Futatsugi,Suzuka Takahashi

doi:10.1186/ar3620

Ayumi Fukuoka, Kenji Nakanishi + Show 4 more

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https://doi.org/10.1186/ar3620

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Abstract

Fas is a member of the TNF receptor family and crucial for induction of apoptosis. MRL- lpr/lpr mice, which carry a mutation of Fas, spontaneously develop systemic autoimmune disease including arthropathy, indicating that Fas plays an important role in elimination of self-reactive immunocytes by apoptosis. In addition to autoimmune diseases, we found a novel phenotype of FasKO mice exclusively in Balb/c genetic background that is allergic blepharitis. Allergic blepharitis is revealed in Balb/c FasKO mice from 15 week-old and about 85% of the mice suffered from allergic blepharitis at 35 week-old. Serum concentrations of both IgG1 and IgE Abs were about 100-times higher in 20-week old FasKO mice than in WT mice; however, there was no significant difference between WT and FasKO mice in the ability of B cells to produce IgG1 and IgE Abs in the presence of IL-4 and anti-CD40 Ab inducing co-stimulatory signals. Additionally, the production of IL-4 by T cells was same. These results suggested that other type of cells enhanced IgG1 and IgE Abs production from B cells in Balb/c FasKO mice. To identify the cells enhancing IgG1 and IgE Abs production, we cultured B cells in vitro in the presence of IL-4 and anti-CD40 Ab together with various types of cells from Balb/c FasKO mice. In the result, we found FasKO non-T non-B cells upregulated the production of both IgG1 and IgE from B cells. Moreover, the number of these cells was specifically increased in Balb/c FasKO mice.All the results indicate that these cells enhance production of IgG1 and IgE from B cells in the presence of IL-4 and anti-CD40 Ab, and excessive accumulation of these cells may cause allergy via hyper-production of IgE. Figure 1 Balb/c FasKO mice develope allergic blepharitis.

Highlights

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases
tumor necrosis factor (TNF) therapy and demyelinating event: A report indicates that adverse events such as the demyelinating lesion in the brain, optic neuritis, and neuropathy occurred after treatment with anti-TNF alpha therapy in collagen disease, and TNF antagonizing therapy showed worsening in a clinical trial with MS
Believing on the similarities of normal joints in humans and monkeys, we have employed a model of collagen-induced arthritis in Macaca fascicularis in an attempt to evaluate the histological alterations caused by such condition in the extracellular matrix of the articular cartilage

Summary

Introduction

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases. Acute Serum Amyloid A (A-SAA) is an acute phase protein strongly expressed in rheumatoid arthritis (RA) synovial tissue (ST) critically involved in regulating cell migration and angiogenesis These processes are dependent on downstream interactions between extracellular matrix and cytoskeletal components. Conclusions: These results indicate that Egr-1 contributes to IL-1mediated down-regulation of PPARg expression in OA chondrocytes and suggest that this pathway could be a potential target for pharmacologic intervention in the treatment of OA and possibly other arthritic diseases. Immune cell-derived microparticles (MPs) are present at increased amounts in synovial fluid of rheumatoid arthritis (RA) patients [1] and can activate disease-relevant signalling pathways in RA synovial fibroblasts (SF) [2,3].

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