CD200-Fc, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis.

OBJECTIVE: The CD200 receptor (CD200R) is an inhibitory receptor expressed by myeloid cells that is postulated to play an important role in regulation of the immune system. The purpose of this study was to evaluate the efficacy of a soluble ligand of CD200R in established collagen-induced arthritis (CIA) in mice and to analyze changes in cytokine expression following therapy in order to understand its primary mechanism of action. METHODS: Arthritis was induced in DBA/1 mice, and CD200-Fc fusion protein, an isotype control monoclonal antibody, or TNFR-Fc fusion protein was administered over a period of 10 days (total of 4 doses). Cytokine expression in the joint was assessed by flow cytometry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. RESULTS: CD200-Fc significantly reduced the severity of established arthritis at the clinical and histologic levels. The therapeutic effect of CD200-Fc at 1 mg/kg was comparable with that of TNFR-Fc at 4 mg/kg. CD200R was found to be expressed in arthritic synovia and in lymph nodes, yet no changes in T cell cytokine levels (interferon-gamma, interleukin-5 [IL-5], IL-10, IL-17) were detected after CD200-Fc therapy. There was no evidence of an expansion of forkhead box P3-positive regulatory T cells or a change in serum anticollagen IgG1 and IgG2a levels. However, administration of CD200-Fc markedly decreased the expression of messenger RNA for tumor necrosis factor alpha, IL-1beta, IL-10, and matrix metalloproteinase 13 in the joint to the same extent as administration of TNFR-Fc. CONCLUSION: CD200-Fc is an effective therapeutic agent in established CIA that targets proinflammatory cytokine expression in the joint without any obvious systemic immunosuppressive effects. Our findings indicate that CD200-Fc has considerable potential as a novel therapeutic agent in rheumatoid arthritis in humans

Entrepreneurial Competences: Comparing and Contrasting Models and Taxonomies

The emphasis on competencies as capturing key aspects of entrepreneurship is relatively recent and quite distinct from research on entrepreneurial traits or cognitive styles in that competencies represent observable and measurable knowledge, behaviour, attitudes and skills. Many competency taxonomies and models have been proposed by scholars, as frameworks organized into tiers of competencies including descriptions of the activities and behaviours associated with that competency (Chouhan & Srivastava, 2014). However, no comprehensive set of entrepreneurial competencies has emerged from these distinctions and no or little empirical evidence has been provided to validate these categorizations (Morris et al., 2013). This study compares and contrasts three traditional models (Morris et al., 2013, Bartram\u2019s 2005, with the EU Entrepreneurship Competence Framework; EntreComp, Bacigalupo et al., 2016) previously empirically validated by the author