The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier

Macleod, Tom; Berekméri, Anna; Bridgewood, Charlie; Stacey, Martin; McGonagle, Dennis; Wittmann, Miriam

doi:10.3389/fimmu.2021.808012

Cited by 41 publications

(25 citation statements)

References 201 publications

(219 reference statements)

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“…34 The higher levels of several type 2 immunity cytokines in Inuit AD children argue against hypothesis that increased inflammation is accountable for the difference in Staphylococcus colonization. 35 Since expression of staphylococcal adhesins including fibronectin and fibrinogen is stimulated by type 2 immunity cytokines, one would expect that S. aureus colonization in fact was more common in Inuit skin. 36,37 The skin commensals S. hominis and S. epidermidis were more abundant in Inuit AD and healthy skin than Danish AD skin.…”

Section: Discussionmentioning

confidence: 99%

Ethnic endotypes in paediatric atopic dermatitis depend on immunotype, lipid composition and microbiota of the skin

Andersson,

Ingham,

Edslev

et al. 2023

Acad Dermatol Venereol

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BackgroundAtopic dermatitis (AD) endotypes differ with ethnicity. We examined the skin microbiota, cytokine‐, and lipid‐profiles in Greenlandic Inuit and Danish children with AD.Methods25 Inuit children with AD and 25 Inuit control children were clinically examined and compared to previously collected data from 25 Danish children with AD. Skin tape strips and skin swabs were collected from lesional and non‐lesional skin. Levels of cutaneous immune biomarkers, free sphingoid bases and their (glycosyl)ceramides were analyzed. Skin swabs were analyzed with 16S rRNA and tuf gene for characterization of bacterial species communities.ResultsBacterial β‐diversity was significantly different between Inuit and Danish AD skin, in both lesional (p<0.001) and non‐lesional (p<0.001) AD skin, and there was a higher relative abundance of Staphylococcus aureus in Danish compared to Inuit lesional (53% vs. 8%, p<0.01) and non‐lesional skin (55% vs. 5%, p<0.001). Danish AD children had a higher α‐diversity than Inuit children in non‐lesional (p<0.05) but not in lesional skin. Significantly higher levels of type 2 immunity cytokine interleukin (IL)‐4 (p<0.05) and IL‐5 (p<0.01) were identified in Inuit compared to Danish AD children. In contrast, IL‐33 (p<0.01) was higher in Danish lesional and non‐lesional AD skin. Higher levels of long‐chain glucosylceramide (GlcCER)[S](d26:1) were found in lesional (p<0.001) and non‐lesional (p<0.001) Inuit skin compared with Danish AD skin. NMF levels were similar in Inuit and Danish AD skin.ConclusionSkin microbiota, cytokine and lipid composition differed significantly between Inuit and Danish children with AD and showed a stronger type 2 immune signature in Inuit children.

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Section: Discussionmentioning

confidence: 99%

Ethnic endotypes in paediatric atopic dermatitis depend on immunotype, lipid composition and microbiota of the skin

Andersson,

Ingham,

Edslev

et al. 2023

Acad Dermatol Venereol

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“…IL-1 signaling is pivotal in mounting inflammatory responses to eliminate microbial infection and aid in physiological processes such as wound healing 40,41 . Suppression of this pathway by various cell types is critical for resolution of acute inflammatory responses 42,43 .…”

Section: Discussionmentioning

confidence: 99%

Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation

Dhariwala,

DeRogatis,

Okoro

et al. 2023

Preprint

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Early life microbe-immune interactions at barrier surfaces have lasting impacts on the trajectory towards health versus disease. Monocytes, macrophages and dendritic cells are primary sentinels in barrier tissues, yet the salient contributions of commensal-myeloid crosstalk during tissue development remain poorly understood. Here, we identify that commensal microbes facilitate accumulation of a population of monocytes in neonatal skin. Transient postnatal depletion of these monocytes resulted in heightened IL-17A production by skin T cells, which was particularly sustained among CD4+T cells into adulthood and sufficient to exacerbate inflammatory skin pathologies. Neonatal skin monocytes were enriched in expression of negative regulators of the IL-1 pathway. Functional in vivo experiments confirmed a key role for excessive IL-1R1 signaling in T cells as contributing to the dysregulated type 17 response in neonatal monocyte-depleted mice. Thus, a commensal-driven wave of monocytes into neonatal skin critically facilitates long-term immune homeostasis in this prominent barrier tissue.

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“…Interleukin-1α is also suggested to play a role in autoinflammatory diseases, independently of IL-1β [ 1 ]. Interleukin-1α is constitutively expressed by keratinocytes, stored intracellularly and released upon cellular injury [ 91 ]. Extracellular IL-1α regulates the production of granulocyte colony-stimulating factor, IL-6, CXCL-1, and CXCL-8, recruiting and activating neutrophils.…”

Section: Biologicsmentioning

confidence: 99%

Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

Maronese

Pimentel

et al. 2022

Am J Clin Dermatol

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Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.

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The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier

Cited by 41 publications

References 201 publications

Ethnic endotypes in paediatric atopic dermatitis depend on immunotype, lipid composition and microbiota of the skin

Ethnic endotypes in paediatric atopic dermatitis depend on immunotype, lipid composition and microbiota of the skin

Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation

Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

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