Pulmonary CD103+ dendritic cells prime Th2 responses to inhaled allergens

Nakano, Hideki; Free, Meghan E.; Whitehead, Gregory S.; Maruoka, Shuichiro; Wilson, Rhonda H.; Nakano, Keiko; Cook, Donald N.

doi:10.1038/mi.2011.47

Cited by 145 publications

(169 citation statements)

References 55 publications

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“…There has been some debate about which DC subset in the lung contributes to this process. Using ex vivo isolated DCs from the lungs of D. pteronyssinus-challenged mice, Nakano et al (29) showed that CD103 + DCs selectively primed Th2 cells, whereas CD11b + DCs were responsible for Th1 skewing. They substantiated this claim by showing that BXH2 mice, which possess a point mutation in the IRF8 coding region and lack CD103 + DCs, fail to mount a robust Th2 response after D. pteronyssinus treatment.…”

Section: Discussionmentioning

confidence: 99%

“…However, these cells mainly act at the late stage of inflammation by secreting chemokine and presenting Ag within the lung tissue (27). The exact contribution of each lung-resident DC subset to the pathogenesis of dust mite allergy is not conclusive, as studies using ex vivo sorted lung DCs have led to conflicting reports about the contribution of CD103 + and CD11b + DCs to Th2 priming (27)(28)(29). In addition, although mouse models that permit the selective depletion of lung CD103 + DCs exist (30,31), it has only recently been possible to specifically deplete resident lung CD11b + DCs.…”

mentioning

confidence: 97%

“…However, due to conflicting reports (27)(28)(29), which subset of lung-resident DCs is responsible for the induction of Th2 priming remains a subject of debate.…”

Section: In Vivo Depletion Of Cd11bmentioning

confidence: 99%

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GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

Zhou

Schlitzer

et al. 2014

The Journal of Immunology

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The Blomia tropicalis dust mite is prevalent in tropical and subtropical regions of the world. Although it is a leading cause of asthma, little is known how it induces allergy. Using a novel murine asthma model induced by intranasal exposure to B. tropicalis, we observed that a single intranasal sensitization to B. tropicalis extract induces strong Th2 priming in the lung draining lymph node. Resident CD11b+ dendritic cells (DCs) preferentially transport Ag from the lung to the draining lymph node and are crucial for the initiation of Th2 CD4+ T cell responses. As a consequence, mice selectively deficient in CD11b+ DCs exhibited attenuated Th2 responses and more importantly did not develop any allergic inflammation. Conversely, mice deficient in CD103+ DCs and CCR2-dependent monocyte-derived DCs exhibited similar allergic inflammation compared with their wild-type counterparts. We also show that CD11b+ DCs constitutively express higher levels of GM-CSF receptor compared with CD103+ DCs and are thus selectively licensed by lung epithelial-derived GM-CSF to induce Th2 immunity. Taken together, our study identifies GM-CSF–licensed CD11b+ lung DCs as a key component for induction of Th2 responses and represents a potential target for therapeutic intervention in allergy.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

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GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

Zhou

Schlitzer

et al. 2014

The Journal of Immunology

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“…1 DCs, which comprise another lung DC subset, are closely associated with airway epithelium and can prime Th2 differentiation (34). Lower numbers of CD103…”

Section: Discussionmentioning

confidence: 99%

Low Sphingosine-1–Phosphate Impairs Lung Dendritic Cells in Cystic Fibrosis

Krause

Limberis

et al. 2013

Am J Respir Cell Mol Biol

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Dysfunction of the cystic fibrosis transmembrane regulator (CFTR) leads to chronic inflammation and infection of the respiratory tract. The role of CFTR for cells of the pulmonary immune system is only partly understood. The present study analyzes the phenotype and immune stimulatory capacity of lung dendritic cells (DCs) from CFTR knockout (CF) mice. Total numbers of conventional DCs, plasmacytoid DCs, and CD103-positive DCs were lower in CF mice compared with wild-type (WT) control mice, as was the expression of major histocompatibility complex class II molecules (MHCII), CD40, and CD86. After pulmonary infection with respiratory syncytial virus, DC numbers increased in WT mice but not in CF mice, and the T cellstimulatory capacity of CF DCs was impaired. The culture of CF lung DCs with bronchoalveolar lavage fluid (BALF) from WT mice increased the expression of MHCII, CD40, and CD86. The supplementation of CF BALF with sphingosine-1-phosphate (S1P), a mediator of immune cell migration and activation that is decreased in CF BALF, rescued the reduced expression of MHCII and CD40 in WT lung DCs and human blood DCs. These findings suggest that DCs are impaired in the CF lung, and that altered S1P affects lung DC function. These findings provide a novel link between defective CFTR and pulmonary innate immune dysfunction in CF.

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“…3 By contrast, Nakano et al 4 found that CD11b þ CD103 À cells preferentially drive Th1 and CD11b À CD103…”

Section: Introductionmentioning

confidence: 99%

C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma

et al. 2013

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Pulmonary CD103+ dendritic cells prime Th2 responses to inhaled allergens

Cited by 145 publications

References 55 publications

GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

Low Sphingosine-1–Phosphate Impairs Lung Dendritic Cells in Cystic Fibrosis

C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma

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