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Allergic asthma is a chronic inflammatory disease characterized by Th2, conventional dendritic cell (cDC), and B cell activation. In addition to excessive inflammation, asthma pathogenesis includes dysregulation of anti-inflammatory pathways, such as the CD200/CD200R pathway. Thus, we investigated whether a CD200R agonist, CD200Fc, could disrupt the inflammatory cascade in chronic allergic asthma pathogenesis using a mice model of experimental asthma. Mice were exposed to house-dust mite (HDM) for 5 weeks and CD200Fc treatment was initiated after chronic inflammation was established (starting on week 4). We demonstrate that chronic HDM exposure altered CD200 and CD200R expression on lung immune cell populations, including upregulation of CD200 on alveolar macrophages and reduced expression of CD200 on cDC. CD200Fc treatment does not change bronchoalveolar cellular infiltration, however it attenuates B cell activation and skews circulating immunoglobulin profile towards IgG2a. This is accompanied by reduced activation of cDC, including lower expression of CD40, especially on cDC2 CD200R+. Furthermore, we confirm that CD200Fc can directly modulate cDC activation in vitro using bone-marrow derived dendritic cells. Thus, CD200/CD200R pathway is dysregulated during chronic asthma pathogenesis and CD200R agonist modulates B cell and DC activation but, in our chronic model, is not sufficient to alter inflammation measured in bronchoalveolar lavage.

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.