High-Affinity IgE Receptors on Dendritic Cells Exacerbate Th2-Dependent Inflammation

Sallmann, Eva; Reininger, Bärbel; Brandt, Sabine; Duschek, Nikolaus; Hoflehner, Elisabeth; Garner-Spitzer, Erika; Platzer, Barbara; Dehlink, Eleonora; Hammer, Martina; Holcmann, Martin; Oettgen, Hans C.; Wiedermann, Ursula; Sibilia, Maria; Fiebiger, Edda; Rot, Antal; Maurer, Dieter

doi:10.4049/jimmunol.1003392

Cited by 79 publications

(72 citation statements)

References 39 publications

(38 reference statements)

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“…Expression of FcεRI on dendritic cells via genetic modification is sufficient to allow transfected DCs to promote Th2 response and associated pathologies via IgE-dependent mechanism (18,36). DC2 cells found in this study were also loaded with IgE (data not show) probably because of they were isolated from IgE-enriched schistosome infected animals.…”

Section: Discussionmentioning

confidence: 82%

“…A common feature appears that APCs, which can direct Th2 differentiation, are often found among cells positive for FcεRI including basophils (11)(12)(13), mast cells (16,17), and subset of DCs (2,18). We thus at first evaluated and compared the Th2-promoting capacities of FcεRI-positive and FcεRI-negative NBNT cells recovered from S. japonica-infected spleens to identify the cell populations which can independently function as APCs to promote Th2 response in S. japonica infection.…”

Section: Resultsmentioning

confidence: 99%

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IL-4–Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4–Dependent Pathway

Huang

et al. 2015

The Journal of Immunology

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Although dendritic cells (DCs) have been widely demonstrated to play essential roles in initiation of Th2 responses in helminth infections and allergic reactions, the mechanisms remain uncertain largely because DCs do not produce IL-4. In present investigation, we have uncovered a novel subset of DCs from mice infected with Th2-provoking pathogens Schistosoma japonica, which independently promoted Th2 cells via IL-4–dependent pathway. These DCs contained similar levels of IL-4 mRNA and higher levels of IL-12p40 mRNA comparing to basophils, correlating to their Th2-promoting and Th1-promoting dual polarization capacities. Characterized by expression of FcεRI+, these DCs were induced independent of T cells. Further investigations revealed that Th2-promoting FcεRI+ DCs were monocyte-derived inflammatory DCs, which were sufficient to induce Th2 cells in vivo. Egg Ags together with GM-CSF or IL-3 alone were able to stimulate the generation of Th2-promoting FcεRI+ DCs from bone marrow cells in vitro. To our knowledge, our data for the first time demonstrate that IL-4–producing DCs are induced under some Th2-provoking situations, and they should play important roles in initiation of Th2 response.

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Section: Discussionmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

IL-4–Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4–Dependent Pathway

Huang

et al. 2015

The Journal of Immunology

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“…This pathway underlies facilitated antigen presentation, where IgE focuses the allergen on the cell surface through FcεRI. Upon internalisation, the antigen-IgE receptor complex is processed and finally presented through major histocompatibility complex (MHC) class II molecules, lowering the threshold for T-cell activation [19,20] and skewing the polarisation towards Th2 [21]. It was demonstrated that trimeric FcεRI also contributes to clearance of serum IgE, as antigen-IgE complexes are internalised and transferred to lysosomes where they are degraded [22].…”

Section: Role Of Ige and Its Receptorsmentioning

confidence: 99%

Asthma phenotypes and IgE responses

et al. 2015

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The discovery of IgE represented a major breakthrough in allergy and asthma research, whereas the clinical interest given to IgE in asthma has been blurred until the arrival of anti-IgE biotherapy. Novel facets of the complex link between IgE and asthma have been highlighted by the effect of this treatment and by basic research. In parallel, asthma phenotyping recently evolved to the concept of endotypes, relying on identified/suspected pathobiological mechanisms to phenotype patients, but has not yet clearly positioned IgE among biomarkers of asthma.In this review, we first summarise recent knowledge about the regulation of IgE production and its main receptor, FcεRI. In addition to allergens acting as classical IgE inducers, viral infections as well as air pollution may trigger the IgE pathway, notably resetting the threshold of IgE sensitivity by regulating FcεRI expression. We then analyse the place of IgE in different asthma endo/phenotypes and discuss the potential interest of IgE among biomarkers in asthma. @ERSpublications We summarise regulation of IgE production, and discuss IgE in different asthma endo/ phenotypes and among biomarkers

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“…Previous studies have shown that when crosslinked by multivalent antigens, antigen:IgE:FcεRI complexes are rapidly endocytosed by BDCA1 + DCs and monocytes, and the antigens are subsequently presented to T cells (13,14). This antigen presentation has been suggested to significantly contribute to Th2 inflammation associated with allergic diseases (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Serum IgE clearance is facilitated by human FcεRI internalization

Greer¹,

Wu²,

Putnam³

et al. 2014

J. Clin. Invest.

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The high-affinity IgE receptor FcεRI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcεRI is also constitutively expressed in dendritic cells (DCs) and monocytes in humans; however, the specific functions of the FcεRI expressed by these cells are not completely understood. Here, we found that FcεRI expressed by human blood DC antigen 1-positive (BDCA1 + ) DCs and monocytes, but not basophils, traffics to endolysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcεRI on BDCA1 + DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FcεRIα (FCER1A-Tg mice) was endocytosed by conventional DCs and monocytes, and endocytosis was associated with rapid clearance of circulating IgE from these mice. Importantly, this rapid IgE clearance was dependent on monocytes or DCs but not basophils. These findings strongly suggest that constitutive internalization of human FcεRI by DCs and monocytes distinctively contributes to serum IgE clearance.

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High-Affinity IgE Receptors on Dendritic Cells Exacerbate Th2-Dependent Inflammation

Cited by 79 publications

References 39 publications

IL-4–Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4–Dependent Pathway

IL-4–Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4–Dependent Pathway

Asthma phenotypes and IgE responses

Serum IgE clearance is facilitated by human FcεRI internalization

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