Type 2 immunity and inflammation underlie allergic skin disorders, such as atopic dermatitis (AD). In type 2 inflammation, IL-4, IL-13, and IL-5, which are signature type 2 cytokines, are mainly ...produced by type 2 helper T (Th2) cells and form the characteristic features of AD. Epithelial cell-derived cytokines such as IL-25, IL-33, and TSLP initiate type 2 inflammation by modulating various cells, including group 2 innate lymphoid cells. Moreover, IL-31, a newly identified type 2 cytokine produced mainly by Th2 cells, induces pruritus by acting on sensory neurons in the skin. Based on both basic and clinical findings, several biologics targeting Th2 cytokines have been developed and exhibited significant efficacy as therapeutic reagents for AD. We have summarized the roles of each cytokine (IL-4, 5, 13, 25, 31, and 33, and TSLP) in the development of type 2 inflammation, especially AD, from the view of basic studies in mice and clinical trials/observation in humans.
Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, ...randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris.
Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions.
A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups.
No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study.
Abstract Atopic dermatitis (AD), a complex and heterogeneous chronic inflammatory skin disorder, manifests in a spectrum of clinical subtypes. The application of genomics has elucidated the role of ...genetic variations in predisposing individuals to AD. Transcriptomics, analyzing gene expression alterations, sheds light on the molecular underpinnings of AD. Proteomics explores the involvement of proteins in AD pathophysiology, while epigenomics examines the impact of environmental factors on gene expression. Lipidomics, which investigates lipid profiles, enhances our understanding of skin barrier functionalities and their perturbations in AD. This review synthesizes insights from these omics approaches, highlighting their collective importance in unraveling the intricate pathogenesis of AD. The review culminates by projecting future trajectories in AD research, particularly the promise of multi‐omics in forging personalized medicine and novel therapeutic interventions. Such an integrated multi‐omics strategy is poised to transform AD comprehension and management, steering towards more precise and efficacious treatment modalities.
Atopic dermatitis (AD) shows very high prevalence in Asia, with a large unmet need for effective therapeutics. Direct comparisons between European American (EA) and Asian patients with AD are ...unavailable, but earlier blood studies detected increased IL-17+–producing cell counts in Asian patients with AD.
We sought to characterize the Asian AD skin phenotype and compare it with the EA AD skin phenotype.
We performed genomic profiling (real-time PCR) and immunohistochemistry on lesional and nonlesional biopsy specimens from 52 patients with AD (25 EAs and 27 Asians), 10 patients with psoriasis (all EAs), and 27 healthy subjects (12 EAs and 15 Asians).
Although disease severity/SCORAD scores were similar between the AD groups (58.0 vs 56.7, P = .77), greater acanthosis, higher Ki67 counts, and frequent parakeratosis were characteristics of lesional epidermis from Asian patients with AD (P < .05). Most (24/27) Asian patients had high IgE levels. A principal component analysis using real-time PCR data clustered the Asian AD phenotype between the EA AD and psoriasis phenotypes. TH2 skewing characterized both Asian and EA patients with AD but not patients with psoriasis. Significantly higher TH17 and TH22 (IL17A, IL19, and S100A12 in lesional and IL-22 in nonlesional skin; P < .05) and lower TH1/interferon (CXCL9, CXCL10, MX1, and IFNG in nonlesional skin; P < .05) gene induction typified AD skin in Asian patients.
The Asian AD phenotype presents (even in the presence of increased IgE levels) a blended phenotype between that of EA patients with AD and those with psoriasis, including increased hyperplasia, parakeratosis, higher TH17 activation, and a strong TH2 component. The relative pathogenic contributions of the TH17 and TH2 axes in creating the Asian AD phenotype need to be tested in future clinical trials with appropriate targeted therapeutics.
Net Effects of NETs: New Concepts Dainichi, Teruki; Nakajima, Saeko; Iwata, Masashi ...
Journal of investigative dermatology,
20/May , Letnik:
140, Številka:
5
Journal Article
Recenzirano
Odprti dostop
It is challenging to investigate neutrophil extracellular traps (NETs) and bacterial colonization in vivo. Bitschar et al. (2020) oppose an existing paradigm regarding neutrophils in host defense and ...propose that neutrophils increase Staphylococcus aureus skin colonization through NETs, not by trapping microbes but via indirect mechanisms. These results are open to interpretation and should stimulate productive discussions.
The skin is the human body’s largest organ and is home to a diverse and complex variety of innate and adaptive immune functions that protect against pathogenic invasion. Recent studies have ...demonstrated that cutaneous commensal bacteria modulated the host immune system. For example,
Staphylococcus epidermidis
, a skin commensal bacterium, has been demonstrated to induce cutaneous interferon (IFN)-γ- and interleukin (IL)-17A-producing T cells. In addition, cutaneous microbiota changes occur in the chronic inflammatory skin disorders, such as atopic dermatitis, and may influence the activity of skin diseases. In this article, we will review the recent findings related to the interactions of the commensal bacteria with skin homeostasis and discuss the role of the dysbiosis of these bacteria in the pathogenesis of skin diseases.
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