Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge

Abstract

Background-Airway dendritic cells (DC)play an important role in chronic allergic airway inflammation in experimental animals, but a similar role for DC in human allergic asthma has been diYcult to define. This pilot study was undertaken to elucidate the role of DC in allergic asthma by examining their potential to migrate to the lower airways in response to bronchial challenge with specific allergen. Methods-Bronchial biopsy specimens were obtained from seven patients with allergic asthma before and 4-5 hours after allergen challenge. Multicolour immunofluorescence staining was performed on mucosal cryosections to identify changes in the number and phenotypes of DC. Results-A dramatic increase in the number of CD1c+HLA-DR+ DC were observed in the lamina propria after challenge compared with baseline (22.4 v 7.8 cells/mm 2 ). The rapid accumulation (within 4-5 hours) of these cells strongly suggests that they were directly recruited from peripheral blood. Conclusion-We have shown for the first time that a specific DC subset rapidly emigrates into the human bronchial mucosa during allergic inflammation. While this study is based on relatively few patients, the consistency of the overall results strongly suggests that the rapid population dynamics of human airway DC closely parallel those in animal models of acute inflammation. These findings support suggestions that DC have an important role in human airway allergy. (Thorax 2001;56:823-826)

Interactions between epithelial cells and dendritic cells in airway immune responses: lessons from allergic airway disease

“…pDCs were present in low and variable numbers in normal nasal mucosa from unchallenged allergic, and non-allergic, individuals, but cell numbers increased dramatically only after daily provocations for 7 days in allergic subjects and not after shorter exposures as compared to non-allergic subjects. These observations contradict a study by the same authors of the lower airways, where no significant recruitment of pDCs was observed in the lung just 4-5 h after allergen challenge (42). Nor was any increase in the number of CD123 + cells detected at baseline in comparison with nasal biopsies from PAR patients and healthy individuals (41).…”

“…A similar picture emerges for BDCA-1 + myeloid DC (BDCA-1/CD1c + HLA-DR + ) in the lungs of asthmatic patients. Compared to baseline in asthmatic subjects, a rapid increase (within 4-5 h) in the number of BDCA-1 + myeloid DC was observed in the lamina propria after allergen challenge (42). The rapid accumulation of these cells strongly suggests that they are directly recruited from peripheral blood and not formed locally from a resident precursor cell.…”

Anatomical Location Determines the Distribution and Function of Dendritic Cells and Other APCs in the Respiratory Tract

“…The observation of exceptionally rapid turnover rates for RT-DC populations in the mouse is thus far unique to this species. Our earlier studies in the rat (33,46) and humans (47) indicated that this turnover is driven by inhaled irritant (and/or antigenic) stimuli. The exceptional rapidity of this process in the mouse again may be driven by environmental stimuli and may also be a reflection of the high resting respiratory rate in this species, which would result in highly efficient sampling of airborne particles.…”

Leukotriene D4 induces gene expression in human monocytes through cysteinyl leukotriene type I receptor

“…14 Similarly, the activity of both ABCC1 and CysLTs was crucial for CCL19-induced migration of dendritic cells to lymph nodes in vivo in a murine model. 15 In asthmatic patients peripheral blood dendritic cells migrate into the bronchial mucosa during allergic inflammation, 16 and pretreatment with the antileukotriene drug pranlukast significantly attenuates allergen-induced airways responses and alters circulating dendritic cells. 17 Altogether, it seems plausible that CysLTs can play a significant role in monocyte and monocyte-derived dendritic cell migration and differentiation and thereby participate in key aspects of the immune response.…”