As expected, mature DC, for example after activation with CD40L, exhibited suppressed uptake of FITC-dextran (Number 4)

As expected, mature DC, for example after activation with CD40L, exhibited suppressed uptake of FITC-dextran (Number 4). However, DEP improved production of TNF, IL-6, and IFN- (< 0.01), IL-12 (< 0.05), and vascular endothelial growth factor (< 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN- production). CD4+ T cells were not functionally triggered on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser degree CEP) regulate important functional aspects of human being DC, assisting an adjuvant part for this material. Keywords: asthma, allergy, innate immunity, Toll-like receptors, pollution CLINICAL RELEVANCE This study identifies the immunological effects of diesel and car-enriched particulates on dendritic cell activation and their promotion of a Th2-like cytokine response by CD4+ T cells. This is a novel observation relevant to our understanding of the immune adjuvant effects of environmental pollutants and pathogenesis of sensitive pulmonary diseases. Exposure to airborne particulate matter (PM) is definitely firmly linked with the morbidity and mortality from GNF 2 respiratory diseases (1, 2). Ambient airborne particles as well as road traffic pollution are associated with exacerbations of asthma, chronic obstructive pulmonary disease, and allergic rhinitis (1C4). It is hypothesized that airborne PM may contribute to the improved incidence, morbidity, or mortality from asthma in adults and children in urban areas (2). Raises in air pollution levels exacerbate existing airway diseases and are associated with the promotion of sensitive airway diseases (3C7). Diesel exhaust particulates may direct an adjuvant effect by exerting pro-allergic sensitization to generally found environmental allergens (8). Also, exposing mice to PM induces asthma-like conditions, airway responsiveness, and swelling (4, 9). The mechanisms by which PM adversely affects human being health are incompletely recognized. Current thinking is definitely that inhaled PM induces lung swelling, probably in an oxidative stressCdependent manner, by acting on respiratory epithelial or GNF 2 additional cells (4). Dendritic cells (DC) are the GNF 2 sentinel cells of the innate immune system, and developed to rapidly translate varied environmental GNF 2 cues into signals that activate T lymphocytes. Although they are poised to sense and respond to inhaled pollutants, surprisingly little is known about whether and how PM affects the function of DC. Immature DC respond efficiently to danger signals (e.g., endotoxin) such that a primary immune response is appropriately induced (10). Danger signals are transduced by pattern acknowledgement receptors that include the Toll-like receptor (TLR) family (11). Occupation of the TLR by ligand (e.g., lipopolysaccharide [LPS] binding to TLR4) instructs DC to mature (12). DC can also be triggered by T cellCdependent signals such as the ligand for the co-stimulatory receptor CD40 (CD40 ligand, or CD40L). DC maturation is definitely defined by enhanced cell surface manifestation of co-stimulatory molecules, reduced endocytosis, enhanced antigen presentation, activation of T cell proliferation, and improved cytokine production (13C15). Immature DC are specialized for taking up exogenous antigen by mechanisms that include endocytosis (14), yet they exhibit a poor ability to activate T cells unless triggered (16). Lung DC are continually repopulated from circulating progenitors such as monocytes and lineage-committed stem cells, and this can be augmented in response to environmental stimuli (17). Interestingly, PM itself may promote DC recruitment to the lung by inducing secretion of the chemokine MIP-3 (CCL20) from airway epithelial cells (18). Immature DC capture antigen and migrate Rabbit Polyclonal to BL-CAM to the draining lymph nodes. It is thought that maturation takes place during their migration, where DC are now defined as potent stimulators of T cell proliferation having a suppressed ability to take.

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