Decrease of IL-5 Production by Naive T Cells Cocultured with IL-18-Producing BCG-Pulsed Dendritic Cells from Patients Allergic to House Dust Mite

The only currently available anti-tuberculosis vaccine, Bacillus Calmette–Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to reduce IL-5 production and bronchoalveolar eosinophilia in mice. However, their ability to decrease the immune polarization of human Th2 cells is not known. Here, we show that BCG and recombinant BCG producing human IL-18 (rBCG-hIL-18) induced the maturation of Der p 1-stimulated monocyte-derived dendritic cells (MD-DCs) from healthy controls and from patients allergic to house dust mites. After incubation with mycobacteria and Der p 1, MD-DCs produced significantly more IL-23 and IP-10 but had no effect on IL-12p70 or IL-10 production compared to Der p 1-pulsed MD-DCs in the absence of mycobacteria. In the presence of Der p 1, BCG- and rBCG-hIL-18-pulsed MD-DCs cocultured with naive, but not with memory T cells from allergic patients, resulted in a decrease in IL-5 production compared to non-pulsed MD-DCs cultured in the presence of Der p 1. BCG, and especially rBCG-hIL-18, may thus be potential therapeutic tools to reduce exacerbated Th2 responses in patients with allergic asthma.

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Inhaled house dust programs pulmonary dendritic cells to promote type 2 T-cell responses by an indirect mechanism

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00256.2015 ◽

2015 ◽

Vol 309 (10) ◽

pp. L1208-L1218 ◽

Cited By ~ 8

Author(s):

Timothy P. Moran ◽

Keiko Nakano ◽

Gregory S. Whitehead ◽

Seddon Y. Thomas ◽

Donald N. Cook ◽

...

Keyword(s):

Dendritic Cells ◽

Allergic Asthma ◽

House Dust ◽

Lavage Fluid ◽

Th2 Cells ◽

T Helper 2 ◽

Cell Responses ◽

Th2 Responses ◽

Th2 Differentiation

The induction of allergen-specific T helper 2 (Th2) cells by lung dendritic cells (DCs) is a critical step in allergic asthma development. Airway delivery of purified allergens or microbial products can promote Th2 priming by lung DCs, but how environmentally relevant quantities and combinations of these factors affect lung DC function is unclear. Here, we investigated the ability of house dust extract (HDE), which contains a mixture of environmental adjuvants, to prime Th2 responses against an innocuous inhaled antigen. Inhalational exposure to HDE conditioned lung conventional DCs, but not monocyte-derived DCs, to induce antigen-specific Th2 differentiation. Conditioning of DCs by HDE was independent of Toll-like receptor 4 signaling, indicating that environmental endotoxin is dispensable for programming DCs to induce Th2 responses. DCs directly treated with HDE underwent maturation but were poor stimulators of Th2 differentiation. In contrast, DCs treated with bronchoalveolar lavage fluid (BALF) from HDE-exposed mice induced robust Th2 differentiation. DC conditioning by BALF was independent of the proallergic cytokines IL-25, IL-33, and thymic stromal lymphopoietin. BALF treatment of DCs resulted in upregulation of CD80 but low expression of CD40, CD86, and IL-12p40, which was associated with Th2 induction. These findings support a model whereby environmental adjuvants in house dust indirectly program DCs to prime Th2 responses by triggering the release of endogenous soluble factor(s) by airway cells. Identifying these factors could lead to novel therapeutic targets for allergic asthma.

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Th2 polarization by Der p 1–pulsed monocyte-derived dendritic cells is due to the allergic status of the donors

Blood ◽

10.1182/blood.v98.4.1135 ◽

2001 ◽

Vol 98 (4) ◽

pp. 1135-1141 ◽

Cited By ~ 128

Author(s):

Hamida Hammad ◽

Anne-Sophie Charbonnier ◽

Catherine Duez ◽

Alain Jacquet ◽

Geoffrey A. Stewart ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

T Cell ◽

House Dust ◽

House Dust Mite ◽

Th2 Response ◽

Healthy Donors ◽

Dust Mite ◽

Der P 1

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.

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Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2009.12.004 ◽

2010 ◽

Vol 125 (3) ◽

pp. 727-736 ◽

Cited By ~ 36

Author(s):

Valentina Pacciani ◽

Silvia Gregori ◽

Loredana Chini ◽

Stefania Corrente ◽

Marco Chianca ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

House Dust ◽

House Dust Mites ◽

Dust Mites ◽

Suppressor T Cells ◽

Tolerogenic Dendritic Cells ◽

Specific Suppressor T Cells

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PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation

Journal of Experimental Medicine ◽

10.1084/jem.20162069 ◽

2017 ◽

Vol 214 (10) ◽

pp. 3015-3035 ◽

Cited By ~ 52

Author(s):

Samuel Philip Nobs ◽

Sara Natali ◽

Lea Pohlmeier ◽

Katarzyna Okreglicka ◽

Christoph Schneider ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Immune Responses ◽

Inflammatory Diseases ◽

Th2 Cells ◽

M2 Macrophage ◽

Airway Responses

Type-2 immune responses are well-established drivers of chronic inflammatory diseases, such as asthma, and represent a large burden on public health systems. The transcription factor PPARγ is known to promote M2-macrophage and alveolar macrophage development. Here, we report that PPARγ plays a key role in both T cells and dendritic cells (DCs) for development of type-2 immune responses. It is predominantly expressed in mouse Th2 cells in vitro and in vivo as well as human Th2 cells from allergic patients. Using conditional knockouts, we show that PPARγ signaling in T cells, although largely dispensable for IL-4 induction, is critical for IL-33–driven Th2 effector function in type-2 allergic airway responses. Furthermore, we demonstrate that IL-4 and IL-33 promote up-regulation of PPARγ in lung-resident CD11b+ DCs, which enhances migration to draining lymph nodes and Th2 priming capacity. Thus, we uncover a surprising proinflammatory role for PPARγ and establish it as a novel, important mediator of DC–T cell interactions in type-2 immunity.

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SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells

Respiratory Research ◽

10.1186/s12931-021-01757-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yuqing Mo ◽

Ling Ye ◽

Hui Cai ◽

Guiping Zhu ◽

Jian Wang ◽

...

Keyword(s):

T Cells ◽

Allergic Asthma ◽

Cd4 T Cells ◽

Quantitative Polymerase Chain Reaction ◽

Allergic Inflammation ◽

Specific Ige ◽

Th2 Cells ◽

Th1 Cells ◽

Th2 Response ◽

Th1 And Th2

Abstract Background Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells. Methods Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus. Results Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells. Conclusion Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.

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