Facebook: World Allergy Organization
Twitter: World Allergy Organization
LinkedIn: World Allergy Organization
Instagram: World Allergy Organization

IgE and IgE Receptors in ‘Allergic’ Skin Diseases

IgE and IgE Receptors in Atopic Dermatitis

Thomas Bieber
University of Bonn, Germany
Bonn, Germany


In atopic dermatitis, APC such as epidermal Langerhans cells (LC), monocytes and DC express the high-affinity receptor for IgE, FcεRI, which shows several important differences from this receptor on the effector cells of anaphylaxis, i.e. mast cells and basophils . Indeed, it is not constitutively expressed on these cells but seems to be regulated by signals of the inflammatory micromilieu surrounding the cells. Thus, the highest expression of FcεRI is displayed on LC and a recently described inflammatory, dendritic epidermal cell type (IDEC) from lesional skin of atopic dermatitis. The lack or low surface expression of this receptor is due to the low expression of the signal-transducing gamma-chain, which is mandatory for the surface expression, while the IgE-binding alpha-chain is present in a preformed manner inside the cells. This altered regulation of the gamma chain seems to be genetically determined. Furthermore, FcεRI on LC, DC and monocytes lacks the four-transmembrane domain-ß-chain. This has a dramatic functional consequence: in contrast to LC and DC from atopic individuals, normal LC display low FcεRI expression and are not fully activated upon receptor ligation.

Multimeric ligands that have been take up by FcεRI-receptor mediated endocytosis are chanelled efficiently into MHC class II compartments such as organelles in which Cathepsin S dependent processing and peptide loading of newly synthesized MHC class II molecules occurs. This leads to an optimal antigen presentation to T cells, as a first line mechanism for antigen recognition. The expression of high density FcεRI on LC/DC of atopic individuals implies several important features. First, DC extend their ability to react to allergens by binding large amounts of IgE molecules with various specificities. This significantly enhances the probability of cross-linking FcεRI by a defined allergen at the cell surface. Secondly, the IgE/FcεRI complexes allow the capture of rather large allergens which under normal circumstances, are not engulfed efficiently via the usual pathway, i.e. by pinocytosis. Thirdly, aggregation of FcεRI on DC is followed by its internalisation via receptor-mediated endocytosis by coated pits, coated vesicles and endosomes. This route might specifically dictate whether the foreign structure will be efficiently processed and targeted to MHC class II rich compartments, ultimately leading to a higher density of specific peptides in the grooves of surface MHC class II molecules. Finally, DC expressing high receptor densities will display full activation upon FcεRI receptor ligation, most probably inducing the synthesis and release of mediators, which might help to enhance the subsequent antigen presentation.

It cannot be excluded that even complex allergenic structures efficiently captured via FcεRI on DC are processed by these cells in a way leading to the unmasking and presentation of cryptic peptides/epitopes, the T cell never previously encountered including self-proteins having high homology to microbial antigens. This would initiate a primary reaction against these unhidden antigens, thereby helping to increase the variety of the IgE specificities and to mount an IgE response to self proteins.

Antigen uptake and aggregation of FcεRI on LC and IDEC could lead to the de novo synthesis and release of mediators capable of directing T cells toward a defined phenotype and function of Th1 or Th2 cells. Indeed, beside antigen presentation, it appeared that both LC and IDEC exhibit different cytokine profile upon receptor activation. Upon activation via FcεRI, LC do not produce significant amounts of proinflammatory cytokines except for some chemokines like IL-8 and MCP-1. Interestingly LC induce a Th2 like profile in the responding T cells. In contrast to that, FcεRI-induced activation of IDEC leads to the release of a series of pro-inflammatory cytokines and to a Th1 like profile of responding T cells because of the concomitant secretion of IL-12 and IL-18. This is in line with the observation that the initial/acute phase of AD lesions has a Th2 profile while the chronic lesions are more a Th1/Th0 type of inflammation.

More recent findings also strongly suggested that depending on the APC cell type and the maturation stage, FcεRI-mediated allergen uptake and activation leads to signals involved in tolerance induction. Indeed, while in this context LC of the oral mucosa have been shown to secrete IL-10 and TGFß, monocytes from patients with AD produce high amounts of IL-10 and the tryptophan metabolizing enzyme IDO which negatively affect the T cell response. Thus a new picture emerges where FcεRI expressing cells may act as proinflammatory as well as anti-inflammatory players in the complex atopic game.


Bieber T, de la Salle H, Wollenberg A, Hakimi J, Chizzonite R, Ring J et al. Human epidermal langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J Exp Med 1992;175:1285-90.

Grewe M, Bruijnzeel-Koomen CA, Schopf E, Thepen T, Langeveld-Wildschut AG, Ruzicka T et al. A role for th1 and th2 cells in the immunopathogenesis of atopic dermatitis. Immunol Today 1998;19:359-61.

Maurer D, Fiebiger E, Reininger B, Ebner C, Petzelbauer P, Shi GP et al. Fc epsilon receptor I on dendritic cells delivers ige-bound multivalent antigens into a cathepsin S-dependent pathway of mhc class ii presentation. J Immunol 1998;161:2731-9.

Novak N, Bieber T, Katoh N. Engagement of fcepsilonri on human monocytes induces the production of Il-10 and prevents their differentiation in dendritic cells. J Immunol 2001 ;167:797-804.

Novak N, Tepel C, Koch S, Brix K, Bieber T, Kraft S. Evidence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic donors. J Clin Invest 2003;111:1047-56.

Novak N, Valenta R, Bohle B, Laffer S, Haberstok J, Kraft S, Bieber T. FcepsilonRI negagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dnedritic cells induces chemotactic signals and different T-cell phenotypes in vitro. J Allergy Clin Immunol. 2004, 113: 949-57

von Bubnoff D, Matz H, Frahnert C, Rao ML, Hanau D, de la SH et al. FcepsilonRI induces the tryptophan degradation pathway involved in regulating T cell responses. J Immunol 2002;169:1810-6.

Wollenberg A, Wen S, Bieber T. Langerhans cell phenotyping: a new tool for differential diagnosis of inflammatory skin diseases. Lancet 1995;346:1626-7.


Slide presentation

Return to top
Return to WAF: San Antonio index