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2625603 
Journal Article 
Abstract 
Comparative interactions of urban particulate matter with dendritic cells of allergic and non-allergic asthmatic human subjects in vitro 
Williams, MA; Bauer, SM; Walter, S; Georas, S; Lyda, E; Saless, A 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A3784 
English 
WOS:000208771003138 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: The immune pathology of asthma is in part defined by a dysregulated pattern of T cell cytokine secretion and a skewing of the immune response to a Th2 signature (augmented IL-4, IL-5, IL-13 and dampened IFN-γ). Dendritic cells (DC) may be important in the immune-pathogenesis of asthma. In DC from atopic as well as non-atopic asthmatic subjects, we studied their response to ambient urban particulate matter (AUPM) in vitro as compared normal subjects.

Methods: We recruited 25 subjects (10 healthy controls; 9 house-dust mite allergic asthmatic subjects; 6 non-atopic asthmatic subjects) in an RSRB-approved protocol and generated DC from purified blood monocytes. DC function was explored on activation by AUPM and measured by time-dependent endocytosis of exogenous antigen, expression of cell-surface receptors by flow cytometry, secretion of cytokines by multiplex arrays (Bioplex-200, Biorad) and stimulation of alloreactive naive CD4+ T cell proliferation by incorporation of BrdU and Th1/ Th2 cytokine responses.

Results: We found that allergic asthmatic DC exhibited three-fold greater endocytosis of antigen than normals (p<0.05). Stimulation of normal DC with AUPM dampened endocytosis (p<0.05) and expression of the endocytic receptor CD206 while the expression of CD83 was enhanced - concordant with normal maturation of DC. However, allergic asthmatic DC retained a marked ability to endocytose antigen (p<0.05) as well as high expression of CD206 and CD83. This functional disparity between normal and allergic asthmatic DC may be important and is highly unusual. DC from allergic asthmatics also expressed greater levels of the co-stimulatory molecules CD40, CD54 and CD86 (but not CD80) as compared normals (p<0.05) and elevated expression of MHC class I and II (p<0.02) as well as greater levels of TLR2 and TLR4 than normal DC (p= 0.07). Expression of TLR2 and TLR4 was decreased in both groups on activation by AUPM (p<0.01). Moreover, on activation by AUPM, DC from allergic asthmatics secreted a pattern of inflammatory cytokines (TNF, IL-6, IL-8 and IL-10) that was at variance with normal DC. AUPM exposed asthmatic DC, while not as effective as normal DC, stimulated moderate proliferation of naïve CD4+ T cells in co-culture and greater levels of IL-13 as compared normal DC (p<0.01).

Conclusion: The immune pathology of asthma is complex. Our observations suggest a functional dysregulation of allergic asthmatic DC before and after activation by AUPM characterized by sustained endocytosis of antigen, heightened expression of function-associated markers and augmented IL-13 secretion from naïve CD4+ T cells. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010