CD200Fc limits dendritic cell and B cell activation during chronic allergen exposures

Abstract 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.