Lung dendritic cells induce TH17 cells that produce TH2 cytokines, express GATA-3, and promote airway inflammation

Raymond, Marianne; Van, Vu Quang; Wakahara, Keiko; Rubio, Manuel; Sarfati, Marika

doi:10.1016/j.jaci.2011.04.029

Cited by 41 publications

(28 citation statements)

References 49 publications

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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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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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“…Repeated injection of inflammatory DCs i.t. drives triple IL-17 + IL-4 + IL-13 + cells that coexpress Gata-3 and RORgt in lymphoid and lung tissues, which correlates with the development of a severe IgE-independent corticosteroid-resistant airway inflammation (19). Our findings demonstrated that IL-17/ IL-13-producing polyclonal CD47 high T cells represented the progenitors of pathogenic memory T cells, which elicited a Th17/ Th2 cytokine profile in lung tissues.…”

Section: Discussionmentioning

confidence: 57%

“…Twenty-four hours after the last OVA aerosol, phenotypic analysis or cytokine production assays were performed on bronchoalveolar lavage (BAL), lung, and mLN cells. BAL was collected four times with 0.5 ml physiologic saline, and lungs and mLNs were isolated for phenotypic and functional analyses (19).…”

Section: Adoptive Transfer Experimentsmentioning

confidence: 99%

“…For lung explants, lungs were cut into small pieces and cultured for 24 h in RPMI 1640 culture medium (19). IL-4, IL-6, IL-13, IL-17, CCL11/eotaxin (R&D Systems), and thymic stromal lymphopoietin (eBioscience) were measured in lung culture supernatants by ELISA.…”

Section: Cytokine Productionmentioning

confidence: 99%

“…We thus followed polyclonal secondary IR in BALB/c mice that had been immunized and challenged with BMDC-OVA i.t., an experimental model we recently developed that leads to Th17/Th2-associated severe airway inflammation (19). The frequency and absolute numbers of polyclonal secondary effector CD44 high CD4 T cells that expressed a CD47 high phenotype progressively augmented in the mLNs after repeated airway challenge (Fig.…”

Section: Polyclonal Cd47 High T Cells Are the Main Source Of Cytokinementioning

confidence: 99%

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CD47high Expression on CD4 Effectors Identifies Functional Long-Lived Memory T Cell Progenitors

Van

Raymond

Baba

et al. 2012

The Journal of Immunology

Self Cite

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T cell memory is the hallmark of adaptive immunity. Central questions are to determine which cells among proliferating effector T cells will live beyond the crash of the immune response (IR) and develop into functional memory T cells. CD47, considered as a marker of self, is implicated in cell death, cell elimination, and in the inflammatory response. We report in this article that CD47 expression was transiently regulated on Ag-specific CD4 T cells, that is, from CD47high to CD47low to CD47high, during the course of the in vivo IR. Specifically, CD47high status marked central memory CD4 T cell precursors at an early time point of the IR. By contrast, cytokine production was a functional attribute restricted to CD47high, but not CD47low, polyclonal effector CD4 T cells during recall responses in an experimental model of chronic airway inflammatory disease. Passive transfer of CD47high, but not CD47low, CD4 T cells in nonlymphopenic naive mice generated long-lived memory T cells capable of anamnestic responses. We conclude that CD47high status on CD4 T cells identifies functional long-lived memory T cell progenitors.

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Dendritic Cells in Inflammatory Disease

Lambrecht

Guilliams

Hammad

2017

Inflammation - From Molecular and Cellular Mechanisms to the Clinic

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Lung dendritic cells induce TH17 cells that produce TH2 cytokines, express GATA-3, and promote airway inflammation

Cited by 41 publications

References 49 publications

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

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

CD47high Expression on CD4 Effectors Identifies Functional Long-Lived Memory T Cell Progenitors

Dendritic Cells in Inflammatory Disease

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