Sensitization to inhaled antigen by intratracheal instillation of dendritic cells

Lambrecht, Bart N.; Peleman, Renaat; Bullock, Gillian; Pauwels, Romain

doi:10.1046/j.1365-2222.2000.00818.x

Cited by 60 publications

(53 citation statements)

References 41 publications

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“…During the effector phase of the immune response, effector T cells are recruited into the lung and again stimulated by DCs to release cytokines and orchestrate airway inflammation (5,24). The occurrence and the nature of the secondary effector response reflects the character of the primary response and the development of polarized Th1 or Th2 responses during the central processing phase (25). Challenge with aerosolized OVA in mice that were immunized by intratracheal injection of OVA-DC, led to the accumulation of activated CD4 + T lymphocytes in the airways and to eosinophilic airway inflammation and goblet cell hyperplasia, both characteristic of allergic asthma.…”

Section: Discussionmentioning

confidence: 99%

Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation

Lambrecht¹,

Veerman²,

Coyle³

et al. 2000

J. Clin. Invest.

469

444

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Section: Discussionmentioning

confidence: 99%

Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation

Lambrecht¹,

Veerman²,

Coyle³

et al. 2000

J. Clin. Invest.

469

444

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“…In this study, we used in vitro differentiated BMDCs of wild-type (WT), C3aR 2/2 , C5aR1 2/2 , or C3aR 2/2 /C5aR1 2/2 origin as a surrogate for pulmonary cDCs to evaluate the role of AT receptor signaling in cDCs for the development of HDM-induced allergic asthma. BMDCs have been frequently used in the past as a surrogate for pulmonary APCs to study the role of cDCs in asthma development (31)(32)(33)(34)(35). This study has been designed to provide new insights into the role of C3aR and C5aR1 signaling in cDCs on the development of AHR, airway inflammation, mucus production, as well as Th1, Th2, and Th17 cytokine production.…”

Section: /2mentioning

confidence: 99%

Distinct Roles of the Anaphylatoxins C3a and C5a in Dendritic Cell–Mediated Allergic Asthma

Engelke

Wiese

Schmudde

et al. 2014

The Journal of Immunology

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Conventional dendritic cells (cDC) are necessary and sufficient to drive mixed maladaptive Th2/Th17 immune responses toward aeroallergens in experimental allergy models. Previous studies suggest that the anaphylatoxin C3a promotes, whereas C5a protects from the development of maladaptive immunity during allergen sensitization. However, only limited evidence exists that such effects are directly mediated through anaphylatoxin-receptor signaling in cDCs. In this study, we assessed the impact of C3a and C5a on cDC-mediated induction pulmonary allergy by adoptively transferring house dust mite (HDM)–pulsed bone marrow–derived DCs (BMDC) from wild-type (WT) C3aR−/−, C5aR1−/−, or C3aR−/−/C5aR1−/− into WT mice. Transfer of HDM-pulsed WT BMDCs promoted a strong asthmatic phenotype characterized by marked airway resistance, strong Th2 cytokine, and mucus production, as well as mixed eosinophilic and neurophilic airway inflammation. Surprisingly, C3aR−/− cDCs induced a strong allergic phenotype, but no IL-17A production, whereas HDM-pulsed C5aR1−/− cDCs failed to drive pulmonary allergy. Transfer of C3aR−/−/C5aR1−/− cDCs resulted in a slightly reduced allergic phenotype associated with increased IFN-γ production. Mechanistically, C3aR and C5aR1 signaling is required for IL-23 production from HDM-pulsed BMDCs in vitro. Furthermore, C3aR−/− BMDCs produced less IL-1β. The mechanisms underlying the failure of C5aR1−/− BMDCs to induce experimental allergy include a reduced capability to migrate into the lung tissue and a decreased potency to direct pulmonary homing of effector T cells. Thus, we uncovered a crucial role for C5a, but only a minor role for C3a in BMDC-mediated pulmonary allergy, suggesting that BMDCs inappropriately reflect the impact of complement on lung cDC-mediated allergic asthma development.

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“…Asthma phenotype or control mice (n ϭ 5 per group) were surgically anesthetized with ketamine/xylazine, then the skin and musculature over their trachea were carefully reflected surgically, and 1 ϫ 10 5 dendritic cells in 25 l of saline were injected transtracheally using a 30-gauge needle. Dendritic cells given in this fashion have been shown by others to migrate across the airway epithelium, to the draining lymph nodes, where they efficiently present their Ags for sensitization of the treated animals (22)(23)(24). The cutaneous incisions in our animals were closed with surgical staples.…”

Section: Animal Sensitization and Challengementioning

confidence: 99%

“…Although we did not assess trafficking of our cells in vivo, others have shown that dendritic cells introduced into the airways traverse the airway-epithelial barrier, migrate to the draining lymph nodes, and there successfully present their Ags (e.g., Refs. [22][23][24]. This rapid phase of T cell activation is Ag-specific and does not occur in nondraining lymph nodes or the spleen, but the activated cells do recirculate to other secondary lymphoid organs after a moderate delay (23), and this recirculation leads to subsequent systemic sensitization (22).…”

Section: Figure 5 Cd8␣mentioning

confidence: 99%

CD8α+, but Not CD8α−, Dendritic Cells Tolerize Th2 Responses via Contact-Dependent and -Independent Mechanisms, and Reverse Airway Hyperresponsiveness, Th2, and Eosinophil Responses in a Mouse Model of Asthma

Gordon

Nayyar

et al. 2005

The Journal of Immunology

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Splenic CD8α+ dendritic cells reportedly tolerize T cell responses by inducing Fas ligand-mediated apoptosis, suppressing IL-2 expression, or catabolizing T cell tryptophan reserves through expression of IDO. We report in this study that CD8α+, but not CD8α−, dendritic cells purified from the spleens of normal mice can tolerize the Th2 responses of cells from asthma phenotype mice through more than one mechanism. This tolerance could largely be reversed in vitro by anti-IL-10 or anti-TGFβ Ab treatment. However, loss of direct dendritic cell-T cell contact also reduced tolerance, although to a lesser extent, as did adding the IDO inhibitor 1-methyltryptophan or an excess of free tryptophan to the cultures. Within 3 wk of reconstituting asthma phenotype mice with 1 × 105 OVA-pulsed CD8α+, but not CD8α−, dendritic cells, the mice experienced a reversal of airway hyperresponsiveness, eosinophilic airway responses, and pulmonary Th2 cytokine expression. This data indicates that CD8α+ dendritic cells can simultaneously use multiple mechanisms for tolerization of T cells and that, in vivo, they are capable of tolerizing a well-established disease complex such as allergic lung disease/asthma.

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Sensitization to inhaled antigen by intratracheal instillation of dendritic cells

Cited by 60 publications

References 41 publications

Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation

Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation

Distinct Roles of the Anaphylatoxins C3a and C5a in Dendritic Cell–Mediated Allergic Asthma

CD8α+, but Not CD8α−, Dendritic Cells Tolerize Th2 Responses via Contact-Dependent and -Independent Mechanisms, and Reverse Airway Hyperresponsiveness, Th2, and Eosinophil Responses in a Mouse Model of Asthma

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