Innate Immunity in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic inflammatory skin disease. In AD patients, the combination of a genetic predisposition for skin barrier dysfunction and dysfunctional innate and adaptive immune responses leads to a higher frequency of bacterial and viral skin infections. The innate immune system quickly mobilizes an unspecific, standardized first-line defense against different pathogens. Defects in this system lead to barrier dysfunction which 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. Also, inducible endogenous antibiotics such as the antimicrobial peptides cathelicidin and the beta-defensins may show defective function in lesional AD skin. Eczema herpeticum is a disseminated viral infection almost exclusively diagnosed in AD patients, which is based on unmasking of the viral entry receptor nectin-1, lack of cathelicidin production by keratinocytes, and depletion of Type I IFN-producing plasmacytoid dendritic cells from AD skin. Future therapeutic approaches to AD may include enhancement of impaired innate in addition to downregulation of dysfunctional adaptive immunity.

Hyperactivation of JAK1 tyrosine kinase induces stepwise, progressive pruritic dermatitis

“…As signal transduction by JAK1 involves multiple downstream signaling pathways (42), it is conceivable that the 2 JAK1 mutations, S645P and R878H, promote JAK1 gain of function, but with variably enhanced activation of different downstream signaling pathways. In fact, it has been reported that point mutations such as mice delayed the onset of disease, suggesting the possible importance of some components of the innate immune response in the initiation of dermatitis (38).…”

Complications of atopic dermatitis in childhood

“…Die Beeinträchtigung der Funktion des Stratum corneum (Hauttrockenheit, erhöh-ter pH-Wert) begünstigt die fast obligatorische Kolonisation läsionaler und nichtläsionaler Haut mit mikrobiellen Erregern, insbesondere mit S. aureus. In den letzten Jahren konnte gezeigt werden, dass Patienten mit atopischem Ekzem deutlich geringere Mengen von antimikrobiellen Peptiden in der Epidermis bilden (β-Defensin-2, -3, das Cathelecidin LL-37 und Dermcidin, [34] …”

Schwangerschaftsdermatosen

“…Einzelne Autoren sprechen bei letzteren Patienten von einer "atopic eruption of pregnancy", wobei sich die -durchaus vielgestaltige -Einzelmorphe nicht wesentlich vom breiten Manifestationsspektrum eines normalen AE abhebt [1]. Die Abgrenzung dieser Ekzemmanifestation vom normalen AE als eigenständige Schwangerschaftsdermatose wird daher von uns und anderen nicht nachvollzogen [11,12].…”