Elsevier

Immunobiology

Volume 212, Issue 6, 27 June 2007, Pages 499-503
Immunobiology

The pro- and anti-inflammatory properties of human antigen-presenting cells expressing the high affinity receptor for IgE (FcεRI)

https://doi.org/10.1016/j.imbio.2007.03.001Get rights and content

Abstract

Almost 20 years after the first description of IgE on the surface of epidermal Langerhans cells (LC) and the subsequent characterization of the trimeric FcεRI on human antigen-presenting cells (APC), we have gained profound insights into the receptor responsible for this binding. FcεRI may act as a pro-inflammatory structure on some APC such as inflammatory dendritic epidermal cells (IDEC) in the skin of patients with atopic dermatitis while it can also be an important instrument in mechanisms leading to tolerance on other APC such as LC of the oral mucosa. By virtue of FcεRI, APC can initiate inflammation by secretion of a wide spectrum of pro-inflammatory cytokines and chemokines. FcεRI+DC can induce either Th2 or Th1 profile in T-cells. In contrast, the production of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) as well as IL-10 and TGFß may contribute to the tolerogenic properties of DC.

Introduction

The observation of the presence of IgE molecules on the surface of antigen-presenting cells (APC) in atopic dermatitis has led to the assumption that these cells express some specific receptors able to bind immunoglobulin E (Bieber et al., 1989a; Bruynzeel-Koomen et al., 1986; Leung et al., 1987). This paradigmatic disease became the focus of research because it appeared as a unique pathological situation in patients who are prone to develop on one hand: (i) an increased production of antigen or allergen specific IgE and allergic asthma or rhinitis and on the other hand (ii) a chronic inflammatory skin disease, which is mediated by APC and T-cells. Thus, the description of IgE molecules on the surface of Langerhans cells (LC) in the skin in patients with atopic dermatitis (Bieber and Braun-Falco, 1991; Bieber et al., 1989a; Bruynzeel-Koomen et al., 1986) was a starting point of a series of research programs aimed to identify the structure responsible for this binding. Interestingly, animal models were not useful in this situation since dendritic cells from rodents do not express IgE-binding structures on dendritic cells, even in the context of inflammation. While besides the low affinity receptor for IgE, FcεRII/CD23 (Bieber et al., 1989b), and the IgE binding lectin galectin-3 (Bieber, 1992) have been described on the surface of epidermal LC in AD patients, it appeared that the relevant structure for IgE binding on these cells is the high affinity receptor for IgE FcεRI (Bieber et al., 1992; Klubal et al., 1997; Wang et al., 1992), which belongs to the family of multi-chain immune recognition receptors (MIRR) (Sigalov, 2004). In contrast to the receptor expressed on effector cells of anaphylaxis, i.e. basophils and mast cells, the receptor expressed on APC lacks the classical ß-chain. The lack of this chain seems to confer to the receptor on APC different biological characteristics, e.g. high variability in the receptor expression and its regulation and other properties in terms of down-stream signal transduction machinery (Bieber et al., 1996). One of the major aspects of this receptor expressed on antigen cells is the fact that, in contrast to mast cells and basophils, it is not constitutively expressed, at least on dendritic cells of the skin (Kraft et al., 1998). Constitutive expression can, however, be found on the surface on plasmacytoid dendritic cells in the blood (Novak et al., 2004) and dendritic cells in the oral and nasal mucosa (Allam et al., 2003, Allam et al., 2006). The reason for this discrepancy is currently not known. Concerning dendritic cells and LC most specifically in the skin, the expression and its increase on the surface of these cells is strongly related to distinct type of inflammatory status (Bieber and Braun-Falco, 1991). This is due to the fact that the α-chain seems to be preformed in the cells while the mandatory γ-chain is only up-regulated in the context of inflammation in atopic patients (Kraft et al., 1998; Novak et al., 2003).

Section snippets

FcεR1 as a crucial structure for antigen uptake and presentation

Since dendritic cells are highly specialized APC, it is not surprising that the receptor for IgE may be involved in antigen or allergen uptake via specific IgE molecules (Mudde et al., 1990). Interestingly, the presence of specific IgE and the receptor on the surface of dendritic cells increases the efficiency of antigen uptake and presentation by 100–1000 fold (Bieber, 1997). This may be of great importance in the context of allergen challenge on the skin, since even small amounts of allergens

FcεR1+ dendritic cells may be major players in a generation of atopic inflammation

A detailed analysis of the dendritic cell population in atopic skin has revealed two different types of epidermal dendritic cells in atopic individuals. Besides the classical LC, another cell type has been described and the name “inflammatory dendritic epidermal cells” (IDEC) has been coined for this new cell type (Wollenberg et al., 1996). Their high expression for the receptor is specific for AD (Wollenberg et al., 1999). IDEC can be generated in vitro under reducing conditions (Novak et al.,

Evidence for a role of FcεR1+ dendritic cells in the induction of allergen-specific tolerance

In recent years, strong evidence was provided that some dendritic cells are major contributors in the induction of tolerance. In this context, the role of the high affinity receptor for IgE in the induction of allergen-specific tolerance has been considered. There are at least three lines of evidence supporting this assumption.

  • 1.

    The activation of monocytes and monocyte-derived dendritic cells expressing the FcεRI leads to the production of high amounts of IL-10 (Novak et al., 2001). This

Conclusion and perspectives

Almost 20 years after the first description of IgE on the surface of epidermal LC, we have gained profound insights into the receptor responsible for this binding. The most striking feature of this structure is its variable expression, which seems to depend on the type of APC, the status of the atopic individual, and the micromilieu in which the cell is localized. Thus, the IgE receptor may act as a pro-inflammatory structure on some APC while it can also be an important instrument in

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