Cell Surface Expression of HLA-Cw6 by Human Epidermal Keratinocytes: Positive Regulation by Cytokines, Lack of Correlation to a Variant Upstream of HLA-C

Bogaard, Ellen H. van den; Tijssen, Henk; Rodijk-Olthuis, Diana; Houwelingen, K.P. van; Coenen, Marieke J. H.; Marget, Matthias; Schalkwijk, Joost; Joosten, Irma

doi:10.1016/j.jid.2016.05.112

Cited by 6 publications

(5 citation statements)

References 15 publications

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“…Perturbation of MHC related genes has been used for establishing animal model of models of psoriasis 60 – 63 . The increased expression of MHC-related molecules in human local resident skin cells, especially, HLA-C, may be crucial for transforming the acute inflammation into a chronic disease 64 , which is possibly a key element for building the mouse model of psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells

et al. 2021

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Psoriasis is the most common skin disease in adults. Current experimental and clinical evidences suggested the infiltrating immune cells could target local skin cells and thus induce psoriatic phenotype. However, recent studies indicated the existence of a potential feedback signaling loop from local resident skin cells to infiltrating immune cells. Here, we deconstructed the full-thickness human skins of both healthy donors and patients with psoriasis vulgaris at single cell transcriptional level, and further built a neural-network classifier to evaluate the evolutional conservation of skin cell types between mouse and human. Last, we systematically evaluated the intrinsic and intercellular molecular alterations of each cell type between healthy and psoriatic skin. Cross-checking with psoriasis susceptibility gene loci, cell-type based differential expression, and ligand-receptor communication revealed that the resident psoriatic skin cells including mesenchymal and epidermis cell types, which specifically harbored the target genes of psoriasis susceptibility loci, intensively evoked the expression of major histocompatibility complex (MHC) genes, upregulated interferon (INF), tumor necrosis factor (TNF) signalling and increased cytokine gene expression for primarily aiming the neighboring dendritic cells in psoriasis. The comprehensive exploration and pathological observation of psoriasis patient biopsies proposed an uncovered immunoregulatory axis from skin local resident cells to immune cells, thus provided a novel insight for psoriasis treatment. In addition, we published a user-friendly website to exhibit the transcriptional change of each cell type between healthy and psoriatic human skin.

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Section: Discussionmentioning

confidence: 99%

Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells

et al. 2021

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“…We did not observe nonadditive effects of the risk variants (P nonadditive > 0.43). Although localization of HLA-C*06:02 to specific amino acid positions of HLA-C is known to be difficult (Clop et al, 2013;van den Bogaard et al, 2016;Vince et al, 2016), PsV risk amino acid polymorphisms of HLA-A Cys99 and HLA-DQb1 Asp57 were located at functional pockets of HLA-A and HLA-DQ molecules (Figure 3), suggesting their biological impacts.…”

Section: Hla Imputation Of the Psv Gwas Datamentioning

confidence: 99%

Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese

Hirata

Hirota

Ozeki

et al. 2018

Journal of Investigative Dermatology

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Psoriasis vulgaris (PsV) is an autoimmune disease of skin and joints with heterogeneity in epidemiologic and genetic landscapes of global populations. We conducted an initial genome-wide association study and a replication study of PsV in the Japanese population (606 PsV cases and 2,052 controls). We identified significant associations of the single nucleotide polymorphisms with PsV risk at TNFAIP3-interacting protein 1and the major histocompatibility complex region (P = 3.7 × 10 and 6.6 × 10, respectively). By updating the HLA imputation reference panel of Japanese (n = 908) to expand HLA gene coverage, we fine-mapped the HLA variants associated with PsV risk. Although we confirmed the PsV risk of HLA-C*06:02 (odds ratio = 6.36, P = 0.0015), its impact was relatively small compared with those in other populations due to rare allele frequency in Japanese (0.4% in controls). Alternatively, HLA-A*02:07, which corresponds to the cysteine residue at HLA-A amino acid position 99 (HLA-A Cys99), demonstrated the most significant association with PsV (odds ratio = 4.61, P = 1.2 × 10). In addition to HLA-A*02:07 and HLA-C*06:02, stepwise conditional analysis identified an independent PsV risk of HLA-DQβ1 Asp57 (odds ratio = 2.19, P = 1.9 × 10). Our PsV genome-wide association study in Japanese highlighted the genetic architecture of PsV, including the identification of HLA risk variants.

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“…The host gene of chr6:31238920-31324013-was HLA-C, which plays an important role in the human immune system. The high cellsurface expression of HLA-C was related to aggravating cytotoxic T-cell responses (19). Hsa_circ_0006867 was downregulated in OLP and was derived from LRBA.…”

Section: Discussionmentioning

confidence: 99%

Expression profile of circular RNAs in oral lichen planus

Song¹,

Xu²,

Shao³

et al. 2021

Ann Palliat Med

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Background: This study sought to identify the circular RNAs (circRNAs) differentially expressed in oral lichen planus (OLP) to investigate the possible role of circRNAs in this disease's pathogenesis.Methods: Six OLP and six normal oral mucosal tissues were used for circRNA detection and sequencing.10 selected circRNAs were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted micro (mi)RNAs and messenger (m)RNAs of circRNAs, and competing endogenous (ce)RNA networks were mapped.Results: One hundred and thirty-five circRNAs were identified differentially expressed in OLP tissues compared to normal control tissues, including 83 upregulated circRNAs, and 52 down-regulated circRNAs.RT-qPCR confirmed that 10 circRNAs were all abnormally expressed in OLP. The GO functional analysis and KEGG pathway analysis showed that differentially expressed circRNAs were involved in 535 GO functional items and 78 signal pathways. A ceRNA network analysis showed that circRNAs might interact with a variety of miRNAs.Conclusions: This study mapped the expression profile of abnormally expressed circRNAs in OLP tissues for the first time and showed that circRNAs appear to play an important role in the pathogenesis of OLP.

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Cell Surface Expression of HLA-Cw6 by Human Epidermal Keratinocytes: Positive Regulation by Cytokines, Lack of Correlation to a Variant Upstream of HLA-C

Cited by 6 publications

References 15 publications

Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells

Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells

Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese

Expression profile of circular RNAs in oral lichen planus

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