The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure

MAIT cells : not just another brick in the wall

status: publishe

Severity Classification of Laboratory Animal Procedures in Two Belgian Academic Institutions

According to the EU Directive 2010/63, all animal procedures must be classified as non-recovery, mild, moderate or severe. Several examples are included in the Directive to help in severity classification. Since the implementation of the Directive, different publications and guidelines have been disseminated on the topic. However, due to the large variety of disease models and animal procedures carried out in many different animal species, guidance on the severity classification of specific procedures or models is often lacking or not specific enough. The latter is especially the case in disease models where the level of pain, suffering, distress and lasting harm depends on the duration of the study (for progressive disease models) or the dosage given (for infectious or chemically induced disease models). This, in turn, may lead to inconsistencies in severity classification between countries, within countries and even within institutions. To overcome this, two Belgian academic institutions with a focus on biomedical research collaborated to develop a severity classification for all the procedures performed. This work started with listing all in-house procedures and assigning them to 16 (sub)categories. First, we determined which parameters, such as clinical signs, dosage or duration, were crucial for severity classification within a specific (sub)category. Next, a severity classification was assigned to the different procedures, which was based on professional judgment by the designated veterinarians, members of the animal welfare body (AWB) and institutional animal ethics committee (AEC), integrating the available literature and guidelines. During the classification process, the use of vague terminology, such as ‘minor impact’, was avoided as much as possible. Instead, well-defined cut-offs between severity levels were used. Furthermore, we sought to define common denominators to group procedures and to be able to classify new procedures more easily. Although the primary aim is to address prospective severity, this can also be used to assess actual severity. In summary, we developed a severity classification for all procedures performed in two academic, biomedical institutions. These include many procedures and disease models in a variety of animal species for which a severity classification was not reported so far, or the terms that assign them to a different severity were too vague

Integrating the pathogenesis of spondyloarthritis: gut and joint united?

Purpose of review : The association between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) is well known. Additionally, about half of SpA patients show microscopic gut inflammation. Substantial progress has been made in understanding the pathogenesis of SpA and IBD, with new therapeutic targets for either of them in clinical development. Recent findings : Microscopic gut inflammation was found in early forms of SpA in about 50% of cases and is associated with age, sex, disease activity and degree of MRI inflammation on sacroiliac joints. Although prospective follow-up data in men and murine animal studies show a parallelism between gut and joint evolution in SpA, therapeutic outcomes are not always the same in SpA and IBD. These differences can be ascribed to differences in not only the cytokine pathways and cells involved in disease, tissue localization and environmental factors but also in pharmacokinetics and biodistribution. Summary : A significant amount of data all point in the direction of arthritis and gut inflammation being pathogenetically closely linked in the SpA concept. However, when it comes to therapeutic effectiveness, the gut and the joints do not always react in the same way. These differences in therapeutic effect could be attributed to the different ways in which cytokine pathways are involved in SpA and IBD

The role of the microbiome in gut and joint inflammation in psoriatic arthritis and spondyloarthritis

Spondyloarthiltis (SpA) encompasses a group of diseases characterized by an inflammatory arthritis involving both joints and entheses. However extraarticular symptoms constitute a large element of the pathology and should not be underestimated. Microscopic gut inflammation is observed in 50% of patients with SpA and has been linked to disease activity, underscoring the effect of gut inflammation in SpA. In this review, we discuss the influence of gut microbiota on SpA pathogenesis. A change m microbiota composition has been linked to the development of various inflammatory arthriti des, and dysbiosis is a potential factor in the pathogenesis of multiple inflammatoty diseases. In this context, several groups have reported the modulatory effects of gut microbiota-derived metabolites on the effect of immune cells. The gut mucosa is populated by several types of regulatory T cells, but also some specialized unconventional innate-like T cells. These cells are predominantly found at mucosal and epithelial barrier sites, wheie they serve an essential lole in modulating host-microbial interplay. Apart from the close association between the composition of the microbiota and inflammatoiy diseases, the therapeutic value of dysbiosis needs further investigation and the identification of a causal inflammatory pathway between gut dysbiosis and musculoskeletal inflammation could revolutionize the therapeutic approach in SpA