Novel Therapeutic Approaches and Targets for the Treatment of Atopic Dermatitis

Pescitelli, Leonardo; Rosi, Elia; Ricceri, Federica; Pimpinelli, Nicola; Prignano, Francesca

doi:10.2174/1389201021666200611112755

Cited by 9 publications

(7 citation statements)

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“…On the other hand, considering that not all patients with AD display filaggrin mutations, a combination of primary and secondary barrier defects underlies the disease process. Thus, the inflammation in AD patients, predominantly characterized by a strong and inappropriate Th2 cell activation [68], affects the integrity of the epidermal barrier on multiple levels. Secondary factors adversely affecting the epidermal barrier integrity are predominant in the pathogenesis of psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Th2 Cytokines Affect the Innate Immune Barrier without Impairing the Physical Barrier in a 3D Model of Normal Human Skin

Donetti

Riva

Indino

et al. 2023

JCM

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(1) Background: Atopic dermatitis is one of the most common inflammatory skin diseases characterized by T helper (Th) 2 and Th22 cells producing interleukin (IL)-4/IL-13 and IL-22, respectively. The specific contribution of each cytokine to the impairment of the physical and the immune barrier via Toll-like receptors (TLRs) is poorly addressed concerning the epidermal compartment of the skin. (2) Methods: The effect of IL-4, IL-13, IL-22, and the master cytokine IL-23 is evaluated in a 3D model of normal human skin biopsies (n = 7) at the air–liquid interface for 24 and 48 h. We investigated by immunofluorescence the expressions of (i) claudin-1, zonula occludens (ZO)-1 filaggrin, involucrin for the physical barrier and (ii) TLR2, 4, 7, 9, human beta-defensin 2 (hBD-2) for the immune barrier. (3) Results: Th2 cytokines induce spongiosis and fail in impairing tight junction composition, while IL-22 reduces and IL-23 induces claudin-1 expression. IL-4 and IL-13 affect the TLR-mediated barrier largely than IL-22 and IL-23. IL-4 early inhibits hBD-2 expression, while IL-22 and IL-23 induce its distribution. (4) Conclusions: This experimental approach looks to the pathogenesis of AD through molecular epidermal proteins rather than cytokines only and paves the way for tailored patient therapy.

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Section: Discussionmentioning

confidence: 99%

Th2 Cytokines Affect the Innate Immune Barrier without Impairing the Physical Barrier in a 3D Model of Normal Human Skin

Donetti

Riva

Indino

et al. 2023

JCM

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“…A phase 3 study demonstrated improvements in pruritus, sleep loss and QoL at week 16, confirming the importance of IL‐31 in itch mediation 255 . Conversely, agents that target Th17/IL‐23 (ustekinumab), 256 IL‐17A (secukinumab), 257 IL‐17A and IL‐17F (bimekizumab) and IL‐22 (fezakinumab) have had limited success, ruling out these cytokines as key players in AD 1,202,258 …”

Section: Treatmentmentioning

confidence: 99%

Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options

Bieber

Paller

Kabashima

et al. 2022

Acad Dermatol Venereol

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Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with a high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD is characterized by a wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms and interactions between genetics, immune system dysregulation and environmental factors. In this review, we describe the diverse cellular and molecular mechanisms involved in AD, including the critical role of T-cell-driven inflammation, primarily via T helper (Th) 2-and Th17derived cytokines, many of which are mediated by the Janus kinase (JAK) signaling pathway. These local inflammatory processes interact with sensory neuronal pathways, contributing to the clinical manifestations of AD, including itch, pain and sleep disturbance. The recent elucidation of the molecular pathways involved in AD has allowed treatment strategies to evolve from broad-acting systemic immunosuppressive therapies to more targeted agents, including JAK inhibitors and cytokine-specific biologic agents. Evidence from the clinical development of these targeted therapies has reinforced and expanded our understanding of the pathophysiological mechanisms underlying AD and holds promise for individualized treatment strategies tailored to specific AD subtypes.

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“…With such information, it will be possible to consider personalized and selective drug strategies (PESCITELLI et al, 2021), minimizing the occurrence of extensive side effects and optimizing therapeutic responses.…”

Section: Phenotype Based Therapymentioning

confidence: 99%

Canine atopic dermatitis: systemic immunomodulatory protocol based on clinical phenotype

2023

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Canine atopic dermatitis (cAD) is a multifactorial allergic disease associated with immune dysfunction and abnormal skin barrier. Several immunological mediators play a role in its pathogenesis. Such molecules are produced by the activation of T helper lymphocytes (Th) through polarization to Th1 and/or Th2, which contributes to different lesion patterns. Acute lesions are mediated by an activation of the Th2 cytokine axis, which clinically induces erythema and pruritus. Conversely, in chronic injuries a mixed immune response of Th1/Th2 cytokines occurs, leading to hyperpigmented and lichenified skin. The clinical understanding of these patterns and the mode of action of immunomodulators are crucial for the best clinical management of the atopic patient. In this context, this review discussed the role of the immune response and the immunomodulatory drugs in dogs with atopic dermatitis and suggested a therapeutic protocol based on clinical phenotype. Based on the evidences showed in this review, it is considered appropriate to use immunomodulatory drugs that target cytokine spectrum related with the clinical phenotype of cAD.

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Novel Therapeutic Approaches and Targets for the Treatment of Atopic Dermatitis

Cited by 9 publications

References 0 publications

Th2 Cytokines Affect the Innate Immune Barrier without Impairing the Physical Barrier in a 3D Model of Normal Human Skin

Th2 Cytokines Affect the Innate Immune Barrier without Impairing the Physical Barrier in a 3D Model of Normal Human Skin

Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options

Canine atopic dermatitis: systemic immunomodulatory protocol based on clinical phenotype

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