Accelerated T-cell activation and differentiation of polar subsets characterizes early atopic dermatitis development

Circulating CLA+T cells in atopic dermatitis and their possible role as peripheral biomarkers

“…As AD usually precedes the development of other atopic disorders , these data have important therapeutic implications for treatment of early pediatric AD and possibly prevention of the atopic march, suggesting that early targeting of the Th2/Tc2 axes (i.e., dupilumab) rather than Th22/Tc22 pathways may not only provide a beneficial intervention for children with AD, but also possibly prevent the entire atopic march . Importantly, the most prominent skin‐homing immune alterations (as compared with age‐matched controls) are detected in the very early phase/young pediatric age group (0–3 years old) of AD rather than ‘later’ pediatric stages of 3‐ to 6‐year‐old group . This emphasizes the need to focus on the very young patient group when studying characteristic mechanisms of AD initiation.…”

The skin as an immune organ: Tolerance versus effector responses and applications to food allergy and hypersensitivity reactions

“…When this balance is disturbed, chronic and/or overzealous activation of immune pathways through autoimmunity results in unremitting inflammation, as observed in common skin diseases, including psoriasis (T H 17 centered), cutaneous lupus (T H 1 and interferon centered), 33 and atopic dermatitis (AD; T H 2 centered). 17,[34][35][36][37][38][39][40][41] The latter illustrates the importance and therapeutic potential of the skin as an immune organ: in AD, eosinophils are recruited into the skin by chemokines, including IL-5, and increased T H 2 activation drives production of IL-4 and IL-13, promoting IgE production. This in turn contributes to increased risk of IgE-mediated allergic reactions, food sensitivities, asthma, or autoimmunity.…”

T helper type 2 signatures in atopic dermatitis

“…38,39 The Th2-deviated immune response is demonstrated both in pediatric and adult AD [40][41][42] and is more pronounced in chronic lesions than in acute lesions. 40,43 In addition to The barrier dysfunction is associated with atopic dry skin, increased penetration of allergens, and enhanced Staphylococcus aureus colonization.…”

“…Compiling evidence has shown that acute AD lesions have a significantly greater number of T helper 2 (Th2) cells expressing interleukin-4 (IL-4) and IL-13 compared with normal skin or unaffected AD skin ( Figure 1). 38,39 The Th2-deviated immune response is demonstrated both in pediatric and adult AD [40][41][42] and is more pronounced in chronic lesions than in acute lesions. 40,43 In addition to Th2 deviation, IL-22 produced by Th22 cells is also linked to the chronicity and amplification of atopic inflammation.…”

“…40,43 In addition to Th2 deviation, IL-22 produced by Th22 cells is also linked to the chronicity and amplification of atopic inflammation. 41,43,44 The pathogenic importance of IL-4/IL-13 and IL-22 signaling in AD has recently been demonstrated by the successful improvement in skin inflammation in patients with AD upon treatment with the specific anti-IL-4 receptor α antibody dupilumab and the anti-IL-22 antibody fezakinumab 45,46 Although a potential role for the IL-17-producing Th17 cells has been proposed in AD, 47,48 conflicting results have been reported. 49,50 Despite a low phylogenetic homology of the IL-31 gene in mammals, administration of IL-31 causes an itch response in rodents, dogs, and cynomolgus monkeys.…”