Heller, Nicola

Abstract Eosinophils are a major pathological component of the inflammatory cell infiltrate found in lungs as a result of allergic disease. They migrate into lungs in response to a variety of chemokines. The development and effector phases of the allergic response are dependent on the actions of interleukin (IL)-4 and IL-13 on a wide variety of cell types. However, how these two cytokines directly affect eosinophil signaling, function and chemotaxis is largely unknown. Using mouse eosinophils purified from IL-5 transgenic mice and a transwell migration assay, eotaxin-1 (30nM) induced eosinophil migration 6–11x over background. IL-4 alone was able to induce eosinophil migration 2x over background. More eosinophils migrated in response to eotaxin when IL-14 or IL-13 was also placed in the bottom chamber. IL-4 appeared to be more potent than IL-13. This effect was dependent upon cytokine concentration. Interestingly, when eosinophils were pretreated with IL-4 for 30 minutes prior to chemotaxis, migration to eotaxin-1 was enhanced 4-fold. However, pretreatment with IL-13 did not enhance chemotaxis to eotaxin-1. These data suggest that IL-4 and IL-13 have direct and rapid effects on the chemotactic function of eosinophils with some differences. We are investigating the mechanisms of these effects, as well as other signaling and functional responses of eosinophils to these cytokines. (AI38985 and HLT32007698)

Abstract Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women’s Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions.

Abstract Tissue structural cells are known in some situations to play a role in the presentation of antigen and in immunoregulation. We assessed the expression of B7 homologs, known to be involved in antigen presentation and lymphocyte costimulation, in human airway epithelial cells. Flow cytometry performed on the airway epithelial cell line BEAS-2B, as well as primary bronchial epithelial cells (PBEC), showed that B7-H2 was constitutively expressed on both BEAS-2B and PBEC, whereas B7-1 and B7-2 were undetectable on either epithelial cell type. B7-H2 expression was confirmed by Western blot using a specific antibody. Stimulation with various cytokines, including tumor necrosis factor-α, interferon-γ, and interleukin-4, slightly downregulated B7-H2 expression detected by flow cytometry, but did not significantly alter the apparent level of protein as assessed by Western blotting. Northern blotting detected mRNA for B7-H2 and B7-1, but not B7-2. B7-H2 was cloned from BEAS-2B cells and the sequence verified. Expression of B7-H2 mRNA was detected by real-time reverse transcriptase–polymerase chain reaction in PBEC from three independent donors. Immunohistochemical analysis of airway derived from autopsies revealed expression of B7-H2 in human airway epithelial cells. These results demonstrate that airway epithelial cells express the costimulatory molecule B7-H2, and suggest the possibility that B7-H2 may participate in antigen presentation by epithelial cells.