Expression of High-Affinity IgE Receptor on Human Peripheral Blood Dendritic Cells in Children

Vasudev, Monica; Cheung, Dorothy; Pincsak, H.; Li, Shun-Hwa; Yan, Ke; Simpson, Pippa; Dasu, Trivikram; Grayson, Mitchell H.

doi:10.1371/journal.pone.0032556

Cited by 28 publications

(29 citation statements)

References 25 publications

(36 reference statements)

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“…Moreover, since it is well-known that FcεRI is present not only on mast cells but also on basophils, eosinophils, neutrophils, monocytes, and on different subsets of dendritic cells [43], it may be assumed that IgE may regulate the response of other FcεRI-bearing cells. Indeed, recent studies have indicated that some cellular activities of basophils and dendritic cells are modulated by IgE molecules [44], [45]. Undoubtedly, the repertoire of biological effects elicited by IgE needs to be further clarified.…”

Section: Discussionmentioning

confidence: 99%

IgE by Itself Affects Mature Rat Mast Cell Preformed and De Novo-Synthesized Mediator Release and Amplifies Mast Cell Migratory Response

2013

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BackgroundImmunoglobulin E (IgE) binds to high affinity receptor FcεRI numerously expressed on mast cells. Recent findings have revealed that IgE by itself may regulate various aspects of mast cell biology, however, detailed data is still limited.Methodology/FindingsHere, we have examined the influence of IgE alone, used at different concentrations, on mast cell activity and releasability. For the study we have employed in vivo differentiated mature tissue mast cells isolated from rat peritoneal cavity. Mast cells were exposed to IgE alone and then the release of preformed and de novo-synthesized mediators, surface FcεRI expression and mast cell migratory response were assessed. IgE by itself was found to up-regulate FcεRI expression and activate mast cells to degranulation, as well as de novo synthesis and release of cysteinyl leukotrienes and TNF. We have provided evidence that IgE alone also amplified spontaneous and CCL5- or TNF-induced migration of mast cells. Importantly, IgE was effective only at concentrations ≥ 3 µg/mL. A molecular basis investigation using an array of specific inhibitors showed that Src kinases, PLC/PLA2, MAP kinases (ERK and p38) and PI3K were entirely or partially involved in IgE-induced mast cell response. Furthermore, IgE alone stimulated the phosphorylation of MAP kinases and PI3K in rat mast cells.ConclusionOur results clearly demonstrated that IgE by itself, at higher concentrations, influences mast cell activity and releasability. As there are different conditions when the IgE level is raised it might be supposed that in vivo IgE is one of the important factors modulating mast cell biology within tissues.

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Section: Discussionmentioning

confidence: 99%

IgE by Itself Affects Mature Rat Mast Cell Preformed and De Novo-Synthesized Mediator Release and Amplifies Mast Cell Migratory Response

2013

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“…This translation is just beginning, but it has been shown that the high-affinity IgE receptor is found on human DCs in peripheral blood samples from children as early as one year of age (111). Analysis of the second immune axis is challenging due to the rarity of NKT cells and the need for specific biomarkers of M2 macrophages in lung tissue.…”

Section: Innate Immune Cells and Viral Diseasementioning

confidence: 99%

Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens

Holtzman¹

2012

J. Clin. Invest.

142

119

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Research on the pathogenesis of asthma has traditionally concentrated on environmental stimuli, genetic susceptibilities, adaptive immune responses, and end-organ alterations (particularly in airway mucous cells and smooth muscle) as critical steps leading to disease. The focus of this cascade has been the response to allergic stimuli. An alternative scheme suggests that respiratory viruses and the consequent response of the innate immune system also drives the development of asthma as well as related inflammatory diseases. This conceptual shift raises the possibility that sentinel cells such as airway epithelial cells, DCs, NKT cells, innate lymphoid cells, and macrophages also represent critical components of asthma pathogenesis as well as new targets for therapeutic discovery. A particular challenge will be to understand and balance the innate as well as the adaptive immune responses to defend the host against acute infection as well as chronic inflammatory disease.

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“…However, whether FcεRI on DCs and monocytes is also stabilized by IgE binding is not clearly established. Some studies have shown that surface FcεRI of human blood BDCA1 + DCs and monocytes correlates positively with serum IgE levels (20,21). However, other studies have shown a lack of correlation between IgE levels in blood and FcεRI levels on BDCA1 + DCs or monocytes among individuals with normal ranges of serum IgE levels (8,22).…”

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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Expression of High-Affinity IgE Receptor on Human Peripheral Blood Dendritic Cells in Children

Cited by 28 publications

References 25 publications

IgE by Itself Affects Mature Rat Mast Cell Preformed and De Novo-Synthesized Mediator Release and Amplifies Mast Cell Migratory Response

IgE by Itself Affects Mature Rat Mast Cell Preformed and De Novo-Synthesized Mediator Release and Amplifies Mast Cell Migratory Response

Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens

Serum IgE clearance is facilitated by human FcεRI internalization

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