Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation.

Adipokines as Biomarkers of Atopic Dermatitis in Adults

“…The pathogenesis of eczema remains enigmatic, which hinders treatment modalities [11,12]. A common and long-standing presumption of the essential role of histamine and protease release from mast cells during their allergen-induced immunoglobulin E (IgE)-mediated degradation in evoking skin itch has not stood the test of time in the face of an insufficient therapeutic effect of anti-histamines [13].…”

Going, Toll-like receptors in skin inflammation and inflammatory diseases

“…AD or eczema is a chronic relapsing skin-inflammatory condition derived in response to the defective terminal keratinocyte differentiation and a profound type 2 or Th2 immune response (Brunner et al, 2017[ 17 ]; Drucker et al, 2017[ 38 ]). It is different from psoriasis and also involves Th1, Th9, Th22, and Th17/IL-23 cytokine signaling events described in detail somewhere else (Brunner et al, 2017[ 17 ]; Esaki et al, 2016[ 44 ]; Yang et al, 2020[ 225 ]). It is highly prevalent in both children (15-25 %) and adults (4-7 %) in the USA and is a major health care burden (Esaki et al, 2016[ 44 ]; Silverberg, 2014[ 192 ], 2015[ 193 ]).…”

“…The stimulation of TLR2 in macrophages isolated from AD patients produce a low level of Th1/Th17 cytokines (IFN-γ, IL-12, and IL-17F) but a higher level of Th2 cytokine (IL-15) as compared to macrophages isolated from control human donors (Yang et al, 2020[ 225 ]). However, the continuous activation of TLR2 in AD patients promotes the pro-inflammatory Th1 immune response that increases inflammation at later stages.…”

“…Certain Candida spp. Malassezia and other dermatophytes can infect and reside in atopic skin, and recognition of their PAMPs by TLRs (TLR1, TLR2, and TLR6) may further increase the inflammation (Faergemann, 2002[ 46 ]; Thammahong et al, 2020[ 206 ]; Yang et al, 2020[ 225 ]). Also, HSV-1 infection is common in AD patients, and TLR9 recognizing CpG-sequences of viral DNA may activate MyD88 and TRIF-dependent pro-inflammatory signaling that further enhances skin inflammation in AD patients (David and Longson, 1985[ 34 ]; Wollenberg et al, 2003[ 220 ]).…”

Natural Nrf2 Modulators for Skin Protection

“…Because the skin is a body organ that is directly exposed to the external environment, a special defense strategy is needed for attacks by ultraviolet (UV) rays, contaminants, physical wounds, and biological hazards [ 1 , 2 , 3 , 4 ]. Skin protection is basically dependent on the physical and chemical barrier function of the stratum corneum in the skin [ 5 ]. However, failure of these functions can lead to serious skin diseases and premature skin aging [ 6 ].…”