Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G DOI Creative Commons
Alexander A. Merleev, Antonio Ji‐Xu, Atrin Toussi

et al.

JCI Insight, Journal Year: 2022, Volume and Issue: 7(16)

Published: July 21, 2022

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a posttranslational regulator of the LDL receptor (LDLR). Recent studies have proposed role for PCSK9 in regulating immune responses. Using RNA-Seq–based variant discovery, we identified possible psoriasis-susceptibility locus at 1p32.3, located within (rs662145 C > T). This finding was verified independently acquired genomic and RNA-Seq data sets. Single-cell (scRNA-Seq) keratinocytes as primary source human skin. expression, however, not uniform across keratinocyte subpopulations. scRNA-Seq IHC demonstrated an epidermal gradient PCSK9, with expression being highest basal early spinous layer lowest granular keratinocytes. IL36G followed opposite pattern, siRNA knockdown experiments confirmed this inverse relationship between expression. Other genes were also linked to including IL27RA, IL1RL1, ISG20, STX3. In both cultured nonlesional skin, homozygosity SNP rs662145 T associated lower higher when compared heterozygous skin or cell lines. Together, these results support establish putative link inflammatory cytokine

Language: Английский

Microbiota and maintenance of skin barrier function DOI Open Access
Tamia Harris-Tryon, Elizabeth A. Grice

Science, Journal Year: 2022, Volume and Issue: 376(6596), P. 940 - 945

Published: May 26, 2022

Human skin forms a protective barrier against the external environment and is our first line of defense toxic, solar, pathogenic insults. Our also defines outward appearance, protects internal tissues organs, acts as sensory interface, prevents dehydration. Crucial to skin's function colonizing microbiota, which provides protection pathogens, tunes immune responses, fortifies epithelium. Here we highlight recent advances in understanding how microbiota mediates multiple facets function. We discuss insights into pathological host-microbiota interactions implications for disorders distant organs. Finally, examine microbiota-based mechanisms can be targeted prevent or manage impaired wound healing.

Language: Английский

Citations

360
Novel insights into atopic dermatitis DOI Creative Commons
Charles F. Schuler, Allison C. Billi, Emanual Maverakis

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2022, Volume and Issue: 151(5), P. 1145 - 1154

Published: Nov. 22, 2022

Language: Английский

Citations

122
Exploring the Role of Staphylococcus aureus in Inflammatory Diseases DOI Creative Commons
Huanquan Chen,

Junyan Zhang,

Ying He

et al.

Toxins, Journal Year: 2022, Volume and Issue: 14(7), P. 464 - 464

Published: July 6, 2022

Staphylococcus aureus is a very common Gram-positive bacterium, and S. infections play an extremely important role in variety of diseases. This paper describes the types virulence factors involved, inflammatory cells activated, process host cell death, associated diseases caused by aureus. can secrete enterotoxins other toxins to trigger responses activate cells, such as keratinocytes, helper T innate lymphoid macrophages, dendritic mast neutrophils, eosinophils, basophils. Activated express various cytokines induce response. also death through pyroptosis, apoptosis, necroptosis, autophagy, etc. article discusses MRSA (methicillin-resistant aureus) atopic dermatitis, psoriasis, pulmonary cystic fibrosis, allergic asthma, food poisoning, sarcoidosis, multiple sclerosis, osteomyelitis. Summarizing pathogenic mechanism provides basis for targeted treatment infection.

Language: Английский

Citations

98
S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis DOI Creative Commons
Liwen Deng, Flavia G. Costa,

Kimbria J. Blake

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(24), P. 5375 - 5393.e25

Published: Nov. 1, 2023

Language: Английский

Citations

75
Skin immunity: dissecting the complex biology of our body's outer barrier DOI Creative Commons
Chenlu Zhang, Geil R. Merana, Tamia Harris-Tryon

et al.

Mucosal Immunology, Journal Year: 2022, Volume and Issue: 15(4), P. 551 - 561

Published: March 31, 2022

Our skin contributes critically to health via its role as a barrier tissue, carefully regulating passage of key substrates while also providing defense against exogenous threats. Immunological processes are integral almost every function and paramount our ability live symbiotically with commensal microbes other environmental stimuli. While many parallels can be drawn immunobiology at mucosal sites, immunity demonstrates unique features that relate distinct topography, chemical composition microbial ecology. Here we provide an overview immune organ, reference the broader context immunology. We review paradigms innate well adaptive highlight how skin-specific structures such hair follicles sebaceous glands interact contribute these processes. Finally, for immunology community few emerging areas interest field moving forward.

Language: Английский

Citations

70
Role of IL-36 cytokines in psoriasis and other inflammatory skin conditions DOI Creative Commons

Kacey L. Sachen,

C Greving,

Jennifer E. Towne

et al.

Cytokine, Journal Year: 2022, Volume and Issue: 156, P. 155897 - 155897

Published: June 6, 2022

The IL-36 family of cytokines includes three pro-inflammatory agonists (IL-36α, IL-36β, and IL-36γ) a receptor antagonist (IL-36Ra), which bind signal through heterodimeric composed IL-36R the IL-1R accessory protein (IL-1RAcP). Individuals with inactivating mutations in gene encoding IL-36Ra develop generalized pustular psoriasis, severe form finding clearly links dysregulated pathway activation to inflammatory skin conditions. purpose this review is highlight cellular source cytokines, effects signaling across cell types, association spectrum diseases including various forms psoriasis as well hidradenitis suppurativa, atopic dermatitis, allergic contact dermatitis.

Language: Английский

Citations

65
IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation DOI Creative Commons
Xinhui Ni, Yi Xu, Wang Wang

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(11), P. 1577 - 1587

Published: Oct. 21, 2022

Abstract Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that helicase DDX5 was downregulated from lesions patients with atopic dermatitis and psoriasis, mice keratinocyte-specific deletion of Ddx5 ( ∆KC ) were more susceptible to cutaneous inflammation. Inhibition expression induced by cytokine interleukin (IL)-17D through activation CD93–p38 MAPK–AKT–SMAD2/3 signaling pathway led pre-messenger events favored production membrane-bound, intact IL-36 receptor (IL-36R) at expense soluble IL-36R (sIL-36R) selective amplification IL-36R-mediated responses Restoration sIL-36R experimental or psoriasis suppressed inflammation alleviated disease phenotypes. These findings indicate IL-17D modulation controls during diseases.

Language: Английский

Citations

46
The IL-1 cytokine family as custodians of barrier immunity DOI Creative Commons
Laura Matarazzo, Yasmina Hernandez-Santana, Patrick Walsh

et al.

Cytokine, Journal Year: 2022, Volume and Issue: 154, P. 155890 - 155890

Published: April 21, 2022

The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning innate adaptive immunity genesis inflammation. They widely expressed structural immune cells with marked expression within barrier mucosal surfaces. In lung, gut skin, which common entry sites for pathogens, they play essential functions maintaining functional integrity manage response to insult infections. tissue sites, IL-1 tightly regulated by mechanisms involving decoy protease degradation. Dysregulation these processes associated aberrant inflammation leading a number inflammatory diseases. This review will address roles different at skin surfaces homeostasis, their as mediators diseases such asthma, chronic obstructive pulmonary disease, bowel diseases, atopic dermatitis psoriasis.

Language: Английский

Citations

45
IL-1 Family Cytokines in Inflammatory Dermatoses: Pathogenetic Role and Potential Therapeutic Implications DOI Open Access
Helena Iznardo, L. Puig

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9479 - 9479

Published: Aug. 22, 2022

The interleukin-1 (IL-1) family is involved in the correct functioning and regulation of innate immune system, linking adaptative responses. This complex composed by several cytokines, receptors, co-receptors, all working a balanced way to maintain homeostasis. Dysregulation these processes results tissue inflammation pathogenesis common inflammatory dermatoses such as psoriasis, hidradenitis suppurativa, atopic dermatitis. Therefore, therapeutic targeting IL-1 pathways has been studied, monoclonal antibodies are currently being assessed clinical trials. So far, promising have obtained with anti-IL-36R spesolimab imsidolimab pustular their efficacy tested other conditions.

Language: Английский

Citations

44
Cytokine-Mediated Crosstalk Between Keratinocytes and T Cells in Atopic Dermatitis DOI Creative Commons

Mélanie Humeau,

Katia Boniface, Charles Bodet

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier dysfunction, dysregulated immune response, and dysbiosis with increased Staphylococcus aureus colonization. Infiltration of various T helper cell subsets into lesional subsequent cytokine release are hallmark AD. Release cytokines both cells keratinocytes plays key role in inflammation drives many AD features. This review aims to discuss cytokine-mediated crosstalk between pathogenesis the potential impact virulence factors produced on these interactions.

Language: Английский

Citations

42