Interleukin‐36 cytokines are overexpressed in the skin and sera of patients with bullous pemphigoid

Maglie, Roberto; Mercurio, Laura; Morelli, Martina; Madonna, Stefania; Salemme, Adele; Baffa, Maria Efenesia; Quintarelli, Lavinia; Zenzo, Giovanni M. Di; Antiga, Emiliano; Albanesi, Cristina

doi:10.1111/exd.14791

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…In addition, the role of IL-38 in psoriasis has been extensively explored, with IL-38 expression levels is correlated with the severity of psoriasis. 11,[60][61][62][63][64] Cytokines secreted by Th1 and Th17 cells contribute to the pathogenesis of psoriasis, and IL-38 is involved in regulating the secretion of IL-17 and IL-22 by Th17 cells. 65,66 Moreover, Th17 cells are involved in the progression of various autoimmune diseases, 60,67,68 such as rheumatoid arthritis, 26,36 primary Sjögren's syndrome, 69,70 inflammatory bowel disease, 8 ankylosing spondylitis, 71 allergic rhinitis, 72 glaucoma, 73 septic dermatitis, multiple sclerosis, and autoimmune thyroid disease, [74][75][76][77][78][79][80] suggesting that IL-38 may play a key role in autoimmune diseases.…”

Section: The Role Il-38 In Autoimmune Diseasesmentioning

confidence: 99%

“…In patients with systemic lupus erythematosus (SLE), serum levels of IL‐38 are significantly elevated and its high levels are associated with the remission of SLE‐related symptoms, including proteinuria, leukocyturia and skin lesions, and it has also been reported that IL‐38 is involved in the progression of SLE by regulating the NF‐κB signaling pathway, 57–59 suggesting that IL‐38 may play a play a protective role in SLE. In addition, the role of IL‐38 in psoriasis has been extensively explored, with IL‐38 expression levels is correlated with the severity of psoriasis 11,60–64 . Cytokines secreted by Th1 and Th17 cells contribute to the pathogenesis of psoriasis, and IL‐38 is involved in regulating the secretion of IL‐17 and IL‐22 by Th17 cells 65,66 .…”

Section: Role Of Ll‐38 In Related Diseasesmentioning

confidence: 99%

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The emerging role of IL‐38 in diseases: A comprehensive review

Chen,

Xi,

et al. 2023

Immunity Inflam & Disease

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IntroductionInterleukin‐38 (IL‐38) is a new type of anti‐inflammatory cytokine, which is mainly expressed in the immunity‐related organs and is involved in various diseases including cardiovascular and cerebrovascular diseases, lung diseases, viral infectious diseases and autoimmune diseases.AimThis review aims to detail the biological function, receptors and signaling of IL‐38, which highlights its therapeutic potential in related diseases.ConclusionThis article provides a comprehensive review of the association between interleukin‐38 and related diseases, using interleukin‐38 as a keyword and searching the relevant literature through Pubmed and Web of science up to July 2023.

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Section: The Role Il-38 In Autoimmune Diseasesmentioning

confidence: 99%

Section: Role Of Ll‐38 In Related Diseasesmentioning

confidence: 99%

The emerging role of IL‐38 in diseases: A comprehensive review

Chen,

Xi,

et al. 2023

Immunity Inflam & Disease

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“…A recent study found that NS patients have a predominant IL-36 immune signature ( 30 ), with a clinical trial set to test Spesolimab in NS patients (NCT05856526). Moreover, IL-36 cytokines were overexpressed in BP and PN patient skin ( 31 , 59 ). Similarly, IL-36 expression was associated with inflammation in other eosinophilic disorders (e.g., AR and eosinophilic pustular folliculitis) and induced the in vitro survival, adhesion, migration, and activation of eosinophils, suggesting that IL-36R signaling is an important mediator of eosinophilic responses ( 42 , 60 , 61 ).…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation

Kline,

Orlando,

Lee

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton’s syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

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“…Previous basic research initially investigated the coexisting mechanism of BP and psoriasis. Multiple investigations have shown similar dysregulated cytokine expression and inflammatory responses in the immune systems of psoriasis and bullous pemphigoid patients ( 27 , 31 , 32 ). For instance, IL-1 was found necessary for the development of psoriatic lesions such as epidermal proliferation and differentiation ( 31 ), and the level of IL-1b was found to be higher in blister fluid than in BP serum ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Causal association between psoriasis vulgaris and bullous pemphigoid: a two-sample bidirectional Mendelian randomization study

Zhang,

Yang,

Huang

et al. 2024

Front. Immunol.

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BackgroundThe association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown.ObjectivesTo investigate whether there is a causal effect between psoriasis vulgaris and BP.MethodsTwo-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics for BP were downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 BP cases and 218,066 controls. The GWAS data for psoriasis vulgaris were extracted from Sakaue et al., which comprises 5072 cases and 478,102 controls. Single-nucleotide polymorphisms (SNPs) associated with exposure were selected as instrumental variables by performing additional quality control steps. The inverse-variance-weighted (IVW) method was used for the primary MR analyses, and the MR-Egger regression, weighted mode method, weighted median method, and simple mode were employed for sensitivity analyses. The MR-Egger intercept test and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy and the potentially influential SNPs, respectively.ResultsGenetically determined log odds of psoriasis vulgaris were associated with an increased risk of BP (IVW: odds ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, P=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, P=0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, P=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, P=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, P=0.254) derived directionally consistent relationship between the genetically predicted log odds of psoriasis vulgaris and risks of developing BP. On the contrary, we found that genetically predicted BP had no significant effect on psoriasis vulgaris (IVW: OR=0.996, P= 0.707), indicating the unidirectionality of the relationship. MR-Egger intercept tests showed no evidence of horizontal pleiotropy. No influential SNP driving the results was detected by the leave-one-out sensitivity analysis.ConclusionsOur results suggested that psoriasis vulgaris causally increases the risk of BP, highlighting the need for potential strategies for the prevention and early diagnosis of comorbid BP in patients with psoriasis vulgaris. Further researches into this association and underlying mechanisms are warranted.

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Interleukin‐36 cytokines are overexpressed in the skin and sera of patients with bullous pemphigoid

Cited by 4 publications

References 36 publications

The emerging role of IL‐38 in diseases: A comprehensive review

The emerging role of IL‐38 in diseases: A comprehensive review

Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation

Causal association between psoriasis vulgaris and bullous pemphigoid: a two-sample bidirectional Mendelian randomization study

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