Current Aspects of Innate and Adaptive Immunity in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a highly pruritic, chronic, multifactorial skin disease predisposing to bacterial and viral infections based on abnormalities of the innate and acquired immune system. The innate system quickly mobilizes an inflexible, standardized first-line response against different pathogens. Epidermal barrier dysfunction results in increased protein allergen penetration through the epidermis and predisposes to secondary skin infections. Two loss-of-function mutations in the epidermal filaggrin gene are associated with AD. Langerhans cells and inflammatory dendritic epidermal cells (IDEC) express high affinity IgE receptors, which are functional in IgE-mediated antigen presentation. Inducible antimicrobial peptides including the antiviral cathelicidin and the antibacterial beta-defensins show defective upregulation in lesional AD skin. The desmosomal protein nectin-1 is unmasked in AD lesions, thus becoming a relevant herpes simplex virus (HSV) entry receptor. Type I IFN-producing plasmacytoid dendritic cells are decreased and dysfunctional in AD skin, predisposing the patients to viral skin infections. Molluscum contagiosum virus produces a unique IL-18 binding protein to evade antiviral defense mechanisms. Innate and adaptive immunity do not simply coexist but are linked to one another in a complex network of skin immunobiology.

Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis

“…This implies that AD results from an aberrant adaptive immune response. Yet, the underlying pathogenesis of AD remains largely unknown, and recent evidence suggests that elements of both the innate and adaptive immune systems may play roles in the development of AD [32].…”

Activation of TLR2 Enhances Tight Junction Barrier in Epidermal Keratinocytes

“…If the epidermal barrier is breached by an injury, the invading pathogens are eliminated first by the innate, followed by adaptive immune reactions. The innate immune network of the epidermis consists of a range of pre-existing, rapidly mobilized host defense components, including keratinocytes, neutrophils, mast cells, eosinophils, and macrophages (7). Recognition of pathogens by innate immune cells is mediated by pattern recognition receptors that recognize conserved pathogenassociated molecular patterns.…”

Recent Advances in Mucosal Immunology and Ocular Surface Diseases

“…However, the underlying molecular mechanism by which pollen induces Th2-dominant allergic inflammation via epithelial innate immunity pathways is largely unknown. Substantial evidence now indicates that epithelial cells are central participants in innate and adaptive immune responses [4,5,7]. Based on the observation that we and other groups have made [40,53,54] that TSLP is mainly induced via TLR mediated innate response in epithelia exposed to microbial products, we hypothesized that pollen, such as Ambrosia artemisiifolia short ragweed (SRW), the most widespread plant in North America, may serve as a functional TLR4 agonist that induces production of a proallergic cytokine TSLP via innate immune response to trigger Th2-dominant allergic inflammation.…”