Trends in Immunology
ReviewThe Multi-Modal Immune Pathogenesis of Atopic Eczema
Section snippets
AE: A Complex Disease
AE belongs to the most common human inflammatory diseases, with a prevalence of at least 2–3% in the adult population and 10–30% in infants in the western world. Accordingly, AE has a major impact on total global disease burden [1] and represents a challenge for modern health care systems. Affected patients suffer from acute and often persistent or relapsing eczematous skin lesions that are characterized by erythema, papules, and scaly plaques accompanied by intense pruritus. The underlying
Module 1: The Interplay of Genetic Background and Immunology
The pathogenesis of AE is based on complex genetic traits [7]. Almost 10 years ago a strong association between AE development and loss-of-function mutations in the gene encoding filaggrin was discovered [8]. Filaggrin links keratin filaments with disulfide bonds – a process that leads to epithelial cornification and the generation of a tight physical barrier. In addition, degradation products of filaggrin contribute to skin homeostasis by stabilizing the pH, by ‘moisturing’ the skin, and by
Module 2: The Microbiota and its Role in AE
Analysis of small subunit ribosomal RNA genes (16S rRNA) allows the diversity of microbes in a particular habitat to be assessed [17]. Twin studies using this approach identified interindividual intestinal microbe diversity as well as specific individual bacterial lineages and even similarities among family members [18]. Initial studies comparing cutaneous microbiota also revealed a large inter- and intra-individual diversity [19], and found that gender and exogenous factors such as time since
ILCs: New Players on the Ground
ILCs represent the innate counterpart of T helper cells with comparable cytokine secretion pattern, but lack specific antigen receptors and hematopoietic lineage markers. Similarly to T helper cells, ILC are grouped according to their secreted cytokines into three subsets: ILC1 (IFNγ+), ILC2 (IL-5+, IL-13+) and ILC3 (IL-17+, IL-22+) (reviewed in [42]). Whereas the phenotype and function of mouse ILCs at mucosal surfaces are relatively well understood, understanding their contribution to skin
Module 4: Adaptive Immunity and the Nature of Allergens
Adaptive immunity is activated by the specific recognition of potentially harmful antigens. Whereas in allergic rhinitis misdirected Th2 responses against harmless environmental antigens are directly causative for the symptoms, the contribution of these antigens in AE is under debate. In a subset of newborns and babies a clear association of skin inflammation with ingestion of particular food allergens such as egg, cow milk, or peanut proteins is well established [58], whereas in adults
Concluding Remarks
Dissecting the pathogenesis of AE into different modules allows the heterogeneity of this complex disease to be better characterized. This heterogeneity is increasingly reflected by distinct therapeutic approaches. Therefore, the last section of this review introduces therapeutic strategies and proposes a therapeutic algorithm based on patient stratification (Figure 3). Such an algorithm must recognize the heterogeneity of AE: in some cases causative treatment or even prevention may be
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