<scp>TLR</scp>4‐induced B7‐H1 on keratinocytes negatively regulates <scp>CD</scp>4<sup>+</sup> T cells and <scp>CD</scp>8<sup>+</sup> T cells responses in oral lichen planus

Zhang, Jing; Tan, Ya-Qin; Wei, Minghui; Ye, Xiaojing; Chen, Guanying; Li, Rui; Du, Ge-Fei; Zhou, Gang

doi:10.1111/exd.13244

Cited by 18 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In inflammatory skin disorders such as lichen planus, keratinocytes have been shown to have increased expression of PD‐L1 . This upregulation of PD‐L1 results in deceleration of immune responses to CD8+ T cells . Indeed, PD‐L1 expression on keratinocytes has been implicated in protecting against the development of autoimmunity …”

Section: Discussionmentioning

confidence: 99%

“…10 This upregulation of PD-L1 results in deceleration of immune responses to CD8+ T cells. 11 Indeed, PD-L1 expression on keratinocytes has been implicated in protecting against the development of autoimmunity. 12 Herein, we report a unique presentation of a patient on nivolumab who initially had clinicopathological characteristics consistent with a morbilliform drug eruption which then progressed to TEN over 3 months.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Epidermal programmed cell death‐ligand 1 expression in TEN associated with nivolumab therapy

et al. 2017

View full text Add to dashboard Cite

Nivolumab is a programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening. Here we present a case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma. The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially showed interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal-epidermal junction and an increase of programmed death ligand 1 (PD-L1) expression in both lymphocytes and keratinocytes. Despite treatment with infliximab, high-dose steroids and intravenous immunoglobulin, the patient expired. Herein we describe what we believe is the second case of TEN associated with anti-PD1 therapy reported in the literature. Increased expression of PD-L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti-PD-1 antibody therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epidermal programmed cell death‐ligand 1 expression in TEN associated with nivolumab therapy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Since LPS (the activator of TLR4) and IFN-γ was previously reported to increase the expression of CD274 in oral keratinocytes [ 3 , 27 ], we then explored whether similar effects were detected in epidermal keratinocytes. We demonstrated that IFN-γ could significantly increase CD274 both in protein and mRNA levels in primary human epidermal keratinocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Psoriasis vulgaris is one of the most common forms of psoriasis, which is related to T-lymphocyte infiltration in skin [ 1 ]. CD274, also known as programmed cell death ligand 1 or B7-H1, was reported to inhibit T-cell differentiation and proliferation thus playing a vital role in the regulation of immune reaction [ 2 , 3 ]. It has been proven that the level of CD274 is decreased in the psoriatic epidermis compared with normal epidermis.…”

Section: Introductionmentioning

confidence: 99%

Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing

Xue

et al. 2018

Bioscience Reports

View full text Add to dashboard Cite

It was previously reported that the expression of CD274 was down-regulated in psoriatic epidermis, leading to immune disorders of psoriasis. However, the regulatory mechanisms of CD274 were rarely elucidated. We aimed to explore the regulatory mechanisms of CD274. Skin samples were collected from 18 patients with psoriasis vulgaris and 9 healthy participants for RNA sequencing. Candidate genes were chosen based on degree and k-core difference of genes in the co-expression network. The relations between candidate genes and CD274 were validated by flow cytometry and real-time PCR in primary human epidermal keratinocytes. The therapeutic effect of indirubin was assessed in an imiquimod-treated mouse model. Interferon-γ (IFN-γ), cyclin-dependent kinase (CDK) 1, Toll-like receptor 3 (TLR3), TLR4 and interleukin (IL)-17A were considered as candidate genes. In primary human epidermal keratinocytes, the level of CD274 was obviously increased under the stimulation of IFN-γ and CDK1 inhibitor (indirubin), independent of TLR4, TLR3 or IL-17A. Indirubin alleviated the severity of psoriatic mice in a CD274-dependent manner. Co-expression network analysis served as an effective method for the exploration of molecular mechanisms. We demonstrated for the first time that CD274 was the regulator of indirubin-mediated effect on mouse psoriasis-like skin lesion based on co-expression network analysis, contributing to the alleviation of mouse psoriasis-like skin lesion.

show abstract

“…T lymphocytes are the main types [21,22]. CD4 + T cells and CD8 + T cells should be in dynamic equilibrium in normal immune states [23]. With the progression of LP, the increase in CD4 + T cells and CD8 + T cells is more pronounced.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Immunologic Function Changes in Lichen Planus After Clinical Treatment

et al. 2018

View full text Add to dashboard Cite

BackgroundLichen planus (LP) is a common chronic superficial skin lesion that causes chronic or sub-acute inflammatory disorders. LP can affect the oral cavity, skin, mucous membrane, and other body parts, and features include repeat attacks and long duration, leading to lower quality of life. This study aimed to analyze the changes of immunologic function before and after treatment of LP.Material/MethodsThirty cutaneous LP patients were selected. Peripheral blood was collected in the morning before and after treatment. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient method. Flow cytometry was used to detect T cell subpopulation CD4+ T cells and CD8+ T to calculate CD4+ T/CD8+ T ratio. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the helper T-cell (Th) factor IL-2, IFN-γ, IL-4, IL-6, IL-17, and IL-22 levels.ResultsCompared with before treatment, the expressions of CD4+ T cells and CD8+ T cells were decreased, while the proportion of CD4+ T/CD8+ T were significantly elevated after treatment. IL-2 and IFN-γ secretion were markedly increased, whereas IL-4, IL-6, IL-17, and IL-22 were significantly reduced after treatment (P<0.05).ConclusionsLP treatment reduces the distribution of CD4+ T cells and CD8+ T cells, and promotes the changes of Th1, Th2, and Th17 cytokines secretion.

show abstract

TLR4‐induced B7‐H1 on keratinocytes negatively regulates CD4⁺ T cells and CD8⁺ T cells responses in oral lichen planus

Cited by 18 publications

References 33 publications

Epidermal programmed cell death‐ligand 1 expression in TEN associated with nivolumab therapy

Epidermal programmed cell death‐ligand 1 expression in TEN associated with nivolumab therapy

Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing

Analysis of Immunologic Function Changes in Lichen Planus After Clinical Treatment

Contact Info

Product

Resources

About

TLR4‐induced B7‐H1 on keratinocytes negatively regulates CD4+ T cells and CD8+ T cells responses in oral lichen planus

Cited by 18 publications

References 33 publications

Epidermal programmed cell death‐ligand 1 expression in TEN associated with nivolumab therapy

Epidermal programmed cell death‐ligand 1 expression in TEN associated with nivolumab therapy

Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing

Analysis of Immunologic Function Changes in Lichen Planus After Clinical Treatment

Contact Info

Product

Resources

About

TLR4‐induced B7‐H1 on keratinocytes negatively regulates CD4⁺ T cells and CD8⁺ T cells responses in oral lichen planus