Results of the present study demonstrate that

Results of the present study demonstrate that 25-OHC treatment of THP-1 monocytes induced vimentin intermediate filament reorganization to more cortical structures and a polarized phenotype (Fig. 5). Vimentin is the major intermediate filament protein present in leukocytes and plays an important role in leukocyte motility and endothelial diapedesis [55]. In line, vimentin intermediate filaments play a crucial role during adhesion molecule assembly that is needed during attachment and transendothelial migration [56], an event accompanying the recruitment of circulating monocytes across the tumor vasculature [57]. A characterization of human glioblastoma-associated macrophages revealed that besides lymphocytes and microglia, monocytes/macrophages represent the dominating inflammatory cell population infiltrating these tumors [58]. In summary, data obtained during the present study make it attractive to hypothesize that GBM-derived 25-OHC is able to recruit EBI2-expressing immune brincidofovir australia to the tumor environment. Thereby, 25-OHC may contribute to the recruitment of tumor-associated monocytes/macrophages that are potent modulators of gliomagenesis [59].
Acknowledgments Financial support was provided by the Austrian Nationalbank (Anniversary Fund, project number 14534), the Austrian Research Promotion Agency (FFG; grant No. Bridge P820107), and the Austrian Science Fund (FWF; grant No. F3007, DK-W1241 and W1226, and P22521) and the National Institutes of Neurological Disease and Stroke (NS73831 to PSM). We thank David W. Russell, University of Texas Southwestern Medical Center, Dallas, Texas, USA, for the monoclonal antibody directed against cholesterol 25-hydroxylase.
Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa that persists for at least 12 weeks despite medical therapy and affects up to 10% of the US population., , CRS is often divided into 2 clinically and phenotypically distinct classifications: chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Despite the high incidence of this disease, the pathology of CRS is not well understood, and treatment options are limited, resulting in a significant loss in quality of life and a large financial burden on the health care system. However, it is clear that defects in innate immunity, along with chronic activation of a variety of inflammatory cells, are 2 factors that play roles in the pathogenesis of CRS. B cells are a key component of the adaptive immune response and are known to play several important roles in a variety of inflammatory disorders and at mucosal sites., , In addition to their ability to produce antibodies that contribute to disease pathogenesis, B cells can function as antigen-presenting or regulatory cells and produce a variety of cytokines and chemokines that can influence inflammation. Recently, we have demonstrated that levels of B cell–activating factor of the TNF family, a key B-cell survival factor, are highly increased in nasal polyp (NP) tissue from patients with CRSwNP. Several reports have demonstrated increased levels of various isotypes of immunoglobulins, including IgG, IgE, and IgA, in sinus tissue from patients with CRS., , In addition, we have recently reported increased levels of autoantigen-specific antibodies in NP tissue., Together, these studies suggest that polyp tissue might provide a supportive environment for B-cell survival and antibody production, which can play important roles in the pathogenesis of CRSwNP. EBV-induced protein 2 (EBI2 or GPR183) is known to play a key role in the development of antibody responses in secondary lymphoid organs., Mice deficient in EBI2 have reduced numbers of plasmablasts and, consequently, diminished ability to mount antibody responses after infection., Conversely, mice with B cells that overexpress EBI2 generate massive plasmablast responses at the expense of germinal center B-cell development and have enhanced levels of antibody production., These studies highlight the important role of EBI2 in controlling B-cell responses and antibody production in secondary lymphoid tissues after infection. However, little is known about the role of EBI2 during chronic inflammatory diseases and whether its expression in the periphery might contribute to the generation of pathogenic antibody responses. This study was designed to more fully characterize B-cell responses in the nasal mucosa of patients with CRS and to assess whether EBI2 might play a role in CRS pathogenesis.