scholarly journals Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response

2003 ◽  
Vol 73 (1) ◽  
pp. 91-99 ◽  
Author(s):  
A.-S. Charbonnier
Allergy ◽  
2019 ◽  
Vol 74 (5) ◽  
pp. 976-985 ◽  
Author(s):  
Tadech Boonpiyathad ◽  
Milena Sokolowska ◽  
Hideaki Morita ◽  
Beate Rückert ◽  
Jeannette I. Kast ◽  
...  

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 1135-1141 ◽  
Author(s):  
Hamida Hammad ◽  
Anne-Sophie Charbonnier ◽  
Catherine Duez ◽  
Alain Jacquet ◽  
Geoffrey A. Stewart ◽  
...  

The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC–T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive toDermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite–sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor–α and interleukin (IL)-1β, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite–sensitive patients stimulated by autologous Der p 1–pulsed DCs preferentially produced IL-4 rather than interferon-γ. These effects were abolished in the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite–sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure.


2021 ◽  
Vol 2 ◽  
Author(s):  
Ananth K. Kammala ◽  
Canchai Yang ◽  
Reynold A. Panettieri ◽  
Rupali Das ◽  
Hariharan Subramanian

G protein-coupled receptor kinase 2 (GRK2) is an adapter protein that modulates G protein-coupled receptor (GPCR) signaling. It also regulates the functions and activity of other intracellular proteins in many cell types. Accordingly, GRK2 is thought to contribute to disease progression by a variety of mechanisms related to its multifunctional roles. Indeed, GRK2 levels are enhanced in patient samples as well as in preclinical models of several diseases. We have previously shown that GRK2 regulates mast cell functions, and thereby contributes to exacerbated inflammation during allergic reactions. In the current study, we observed that GRK2 levels are enhanced in the lungs of human asthma patients and in mice sensitized to house dust mite extract (HDME) allergen. Consistent with these findings, interleukin (IL)-4 and IL-13 levels were reduced in the lungs of GRK2+/− mice in a HMDE mouse model of asthma. Because Th2 cells are the major source of these cytokines during asthma, we determined the role of GRK2 in regulating T cell-specific responses in our HMDE mouse model. We observed a significant reduction of airway hyperresponsiveness (AHR), lung eosinophil and lymphocyte counts, serum IgE, Th2 cytokines (IL-4 and IL-13), goblet cell hyperplasia and mucus production in mice that had reduced GRK2 expression specifically in T cells. Collectively, our studies reveal an important role for GRK2 in regulating T cell response during asthma pathogenesis and further elucidation of the mechanisms through which GRK2 modulates airway inflammation will lead to the development of new therapeutic strategies for asthma.


2012 ◽  
Vol 109 (8) ◽  
pp. 3012-3017 ◽  
Author(s):  
L. Cervantes-Barragan ◽  
K. L. Lewis ◽  
S. Firner ◽  
V. Thiel ◽  
S. Hugues ◽  
...  

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