Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.

Cytokine-Mediated Crosstalk Between Keratinocytes and T Cells in Atopic Dermatitis

“…Skin infiltration of various CD4+ Th and CD8+ cytotoxic T cells (Tc) subsets is strongly implicated in AD pathogenesis ( 8 , 10 – 12 ). Atopic skin is characterized by a predominant type 2 immune response, with Th2/Tc2 cells being involved in many features of AD.…”

“…One of the classical features of AD is a strong type 2 immune response that leads to skin barrier dysfunction, such as inhibition of epidermal differentiation and increased skin permeability ( 3 ). Inflammatory cell infiltration found in lesional AD skin is characterized by the presence of type 2 innate lymphoid cells (ILC2) and various T cell subpopulations producing cytokines driving a T helper (Th) type 2-predominant inflammation ( 7 , 8 ). Keratinocytes, the predominant cell type of the epidermis, are also key players in the AD pro-inflammatory environment ( 9 ).…”

Temporal Modulation of Drug Desensitization Procedures

“…Free IgE is constantly present in serum in considerable amounts even in the absence of antigen, with a half-life of 2 days in humans that does not appear to be controlled by a circadian clock [51]. In patients with allergies or atopic diseases, nonetheless, serum IgE levels are markedly increased [52]. In order to keep the number of unoccupied IgE receptor sites at a setpoint, MC may regulate FcεRI expression, possibly in response to the levels of circulating IgE.…”

“…IL-33 can activate both MCs and basophils by means of the receptor ST2. CLOCK, another important clock gene, can gate the MC and basophil response to IL-33 by regulating the rhythmic changes in ST expression [52]. CLOCK also promotes expression of FcεRIβ, an amplifier of FcεRI expression and its downstream signaling [53].…”

Protective Effects of Kyungohkgo on Atopic Dermatitis in HaCaT Cells

“…아토피 피부염은 천식 및 알레르기성 질환에 선행하여 피부 에 만성적으로 재발하는 염증성 질환으로 (Boguniewicz & Leung, 2010), 원인은 정확하게 밝혀지지 않았지만 환경적, 유 전적 요인과 면역조절 불균형 및 피부장벽의 이상 등 다양한 원인에 의해서 발병할 것이라고 추정된다 (Larsen & Hanifin, 2002;Searing & Leung, 2010). 또한, 아토피 피부염의 임상적 특징으로는 심한 가려움증과 함께 동반되는 홍반, 부종, 삼출 및 피부건조와 가피, 인설 등 1차적으로 나타나는 피부손상과 수면장애, 집중력 저하, 정서 불안 등 2차적으로 신체증상이 나 타난다 (Kader et al, 2021). 피부의 가장 표면층인 표피는 다양 한 외부 자극으로부터 체내를 보호하는 장벽기능을 수행하며 표피세포의 형성과 분화, 탈각과정을 반복함으로써 항상성을 유지한다 (Benedetto et al, 2012).…”