Development of house dust mite-induced allergic airway disease in a murine model of sickle cell disease is associated with decreased regulatory cells and increased pulmonary pathology (HYP7P.283)

Abstract

Abstract The hematologic disorder sickle cell disease (SCD) is associated with unusually severe allergic asthma. To explore the mechanisms behind this heightened severity, allergic airway disease was induced in transgenic SCD mice and littermate (LM) controls via 2 wks of intranasal exposure to the clinically-relevant allergen house dust mite (HDM). Following final HDM exposure, animals were sacrificed for pathologic and cellular analyses. SCD was associated with nearly two-fold increase in leukocytes (p < 0.05) and more numerous inflammatory foci in the lung tissue as compared to LM controls. The proportion of CD4+Foxp3+ regulatory T cells was significantly reduced in SCD mice versus LM controls in the broncho-alveolar lavage (BAL) (9% vs. 14% of CD4+ T cells, p < 0.05) and lung (9% vs. 14% of CD4+ T cells, p < 0.01) but not in the hilar (lung-draining) lymph node (HLN). Furthermore, the proportion of CD5+ B cells in SCD mice was nearly half that of LM controls in the BAL (p < 0.0001), lung (p < 0.01), and HLN (p < 0.05). Intriguingly, this B cell population includes regulatory B cells that our laboratory has shown to play an important role in murine models of asthma. The dearth of regulatory cells in SCD may influence the increased pathology seen in the lungs of SCD mice and could contribute to the heightened severity of allergic asthma seen in human SCD. Treatment of asthma in SCD could be enhanced through efforts to target these cellular populations.