Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

Shen, Changbing; Gao, Jing; Yin, Xianyong; Sheng, Yujun; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

doi:10.1016/j.jgg.2015.01.001

Cited by 23 publications

(23 citation statements)

References 45 publications

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“…Members of the LCE3 group of proteins are important for skin barrier repair caused by injury and inflammation (76). Deletion of LCE3B and LCE3C genes in patients is highly associated with the development of psoriasis and other autoimmune diseases (52). Many genes that are dysregulated in psoriasis or other hyperkeratinizing skin disorders are downregulated in our microarray data, in a tissue-specific manner (78).…”

Section: Discussionmentioning

confidence: 89%

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Tissue-Specific Gene Expression during Productive Human Papillomavirus 16 Infection of Cervical, Foreskin, and Tonsil Epithelium

Chatterjee

Kang

Alam

et al. 2019

J Virol

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Epidemiological data confirm a much higher incidence of high-risk human papillomavirus 16 (HPV16)-mediated carcinogenesis of the cervical epithelium than for other target sites. In order to elucidate tissue-specific responses to virus infection, we compared gene expression changes induced by productive HPV16 infection of cervical, foreskin, and tonsil organotypic rafts. These rafts closely mimic persistent HPV16 infection, long before carcinogenesis sets in. The total number of gene expression changes varied considerably across the tissue types, with only 32 genes being regulated in common. Among them, we confirmed the Kelch-like family protein KLHL35 and the laminin-5 complex to be upregulated and downregulated, respectively, in all the three tissues. HPV16 infection induces upregulation of genes involved in cell cycle control, cell division, mitosis, DNA replication, and DNA damage repair in all the three tissues, indicative of a hyperproliferative environment. In the cervical and tonsil epithelium, we observe significant downregulation of genes involved in epidermis development, keratinocyte differentiation, and extracellular matrix organization. On the other hand, in HPV16-positive foreskin (HPV16 foreskin) tissue, several genes involved in interferon-mediated innate immunity, cytokine signaling, and cellular defenses were downregulated. Furthermore, pathway analysis and experimental validations identified important cellular pathways like STAT1 and transforming growth factor β (TGF-β) to be differentially regulated among the three tissue types. The differential modulation of important cellular pathways like TGF-β1 and STAT1 can explain the sensitivity of tissues to HPV cancer progression. IMPORTANCE Although the high-risk human papillomavirus 16 infects anogenital and oropharyngeal sites, the cervical epithelium has a unique vulnerability to progression of cancer. Host responses during persistent infection and preneoplastic stages can shape the outcome of cancer progression in a tissue-dependent manner. Our study for the first time reports differential regulation of critical cellular functions and signaling pathways during productive HPV16 infection of cervical, foreskin, and tonsil tissues. While the virus induces hyperproliferation in infected cells, it downregulates epithelial differentiation, epidermal development, and innate immune responses, according to the tissue type. Modulation of these biological functions can determine virus fitness and pathogenesis and illuminate key cellular mechanisms that the virus employs to establish persistence and finally initiate disease progression.

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Section: Discussionmentioning

confidence: 89%

“…Interestingly, in HPV16 foreskin, only the LCE3 family proteins are downregulated. Deletion of the LCE3B and LCE3C genes is highly associated with a risk of psoriasis development in patients (52).…”

Section: Serum Amyloidmentioning

confidence: 99%

Tissue-Specific Gene Expression during Productive Human Papillomavirus 16 Infection of Cervical, Foreskin, and Tonsil Epithelium

Chatterjee

Kang

Alam

et al. 2019

J Virol

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“…The late cornified envelop gene cluster 3 ( LCE3 ) is part of the epidermal differentiation complex ( EDC ) that encodes stratum corneum proteins in the cornified envelope that have potential functions in epidermal terminal differentiation [29]. LCE3 proteins encompass five genes ( LCE3A, LCE3B, LCE3C, LCE3D, LCE3E ), each with a unique structure and function [30]. Of these genes, deletions of LCE3B and LCE3C (LCE3C_LCE3B-del) are significantly associated with the risk of PsV and PsA [30].…”

Section: Genetic Susceptibility Locimentioning

confidence: 99%

“…LCE3 proteins encompass five genes ( LCE3A, LCE3B, LCE3C, LCE3D, LCE3E ), each with a unique structure and function [30]. Of these genes, deletions of LCE3B and LCE3C (LCE3C_LCE3B-del) are significantly associated with the risk of PsV and PsA [30]. One possibility is that a breach of the skin barrier function allows for a cross-reactive skin/joint immune response to develop.…”

Section: Genetic Susceptibility Locimentioning

confidence: 99%

Interactions of the Immune System with Skin and Bone Tissue in Psoriatic Arthritis: A Comprehensive Review

Sukhov

Adamopoulos

Maverakis

2016

Clinic Rev Allerg Immunol

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Cutaneous psoriasis [e.g. psoriasis vulgaris (PsV)] and psoriatic arthritis (PsA) are complex heterogeneous diseases thought to have similar pathophysiology. The soluble and cellular mediators of these closely related diseases are being elucidated through genetic approaches such as genome-wide association studies (GWAS), as well as animal and molecular models. Novel therapeutics targeting these mediators (IL-12, IL-23, IL-17, IL-17 receptor, TNF) are effective in treating both the skin and joint manifestations of psoriasis, reaffirming the shared pathophysiology of PsV and PsA. However, the molecular and cellular interactions between skin and joint disease have not been well characterized. Clearly, PsV and PsA are highly variable in terms of their clinical manifestations and this heterogeneity can partially be explained by differences in HLA-associations (HLA-Cw*0602 versus HLA-B*27, for example). In addition, there are numerous other genetic susceptibility loci (LCE3, CARD14, NOS2, NFKBIA, PSMA6, ERAP1, TRAF3IP2, IL12RB2, IL23R, IL12B, TNIP1, TNFAIP3, TYK2) and geoepidemiologic factors that contribute to the wide variability seen in psoriasis. Herein we review the complex interplay between the genetic, cellular, ethnic and geographic mediators of psoriasis, focusing on the shared mechanisms of PsV and PsA.

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“…LCE3 gene cluster spans ~60 kb and comprises five genes (LCE3A, 3B, 3C, 3D and 3E) within the EDC (PSORS4) at chromosome 1q21. Because of the strategic role of these genes in epidermal barrier repair and their reported upregulation in psoriatic skin 34 , many later studies focused on the LCE3 genes 35 36 37 38 39 . It has previously been demonstrated that the expression of LCE3 genes were markedly induced after superficial injury of the normal skin 34 40 .…”

mentioning

confidence: 99%

Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population

Chandra

Lahiri

Senapati³

et al. 2016

Sci Rep

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HLA-Cw6 is one of the most associated alleles in psoriasis. Recently, Late Cornified Envelop 3 (LCE3) genes were identified as a susceptibility factor for psoriasis. Some population showed epistatic interaction of LCE3 risk variants with HLA-Cw6, while some population failed to show any association. We determined the associations of a 32.2 kb deletion comprising LCE3C-3B genes and three SNPs (rs1886734, rs4112788; rs7516108) at the LCE3 gene cluster among the psoriasis patients in India. All three SNPs at the LCE3 gene cluster failed to show any association. In contrary, for patients with HLA-Cw6 allele, all three SNPs and the LCE3C-3B deletion showed significant associations. While, all five LCE3 genes were upregulated in psoriatic skin, only LCE3A showed significant overexpression with homozygous risk genotype compared to the non-risk genotype. LCE3B also showed significant overexpression in patients with HLA-Cw6 allele. Moreover, LCE3A showed significantly higher expression in patients bearing homozygous risk genotype in presence of HLA-Cw6 allele but not in those having non-risk genotype, demonstrating the combined effect of HLA-Cw6 allele and risk associated genotype near LCE3A gene. Integration of genetic and gene expression data thus allowed us to identify the actual disease variants at the LCE3 cluster among the psoriasis patients in India.

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Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

Cited by 23 publications

References 45 publications

Tissue-Specific Gene Expression during Productive Human Papillomavirus 16 Infection of Cervical, Foreskin, and Tonsil Epithelium

Tissue-Specific Gene Expression during Productive Human Papillomavirus 16 Infection of Cervical, Foreskin, and Tonsil Epithelium

Interactions of the Immune System with Skin and Bone Tissue in Psoriatic Arthritis: A Comprehensive Review

Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population

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