T cell co-stimulatory and co-inhibitory pathways in atopic dermatitis

Zheng, Chunjiao; Shi, Yujun; Zou, Ying

doi:10.3389/fimmu.2023.1081999

Cited by 10 publications

(5 citation statements)

References 245 publications

(323 reference statements)

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“…Specifically, we observed a standard increase in CD86 signals from myeloid cells to T cells in the SLE, AD, and PS datasets 28 , 29 (Fig. 3 B).…”

Section: Resultsmentioning

confidence: 79%

Gene signature from cutaneous autoimmune diseases provides potential immunotherapy-relevant biomarkers in melanoma

Chun,

Park,

Hwang

et al. 2023

Sci Rep

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Immune checkpoint inhibitors (ICIs) are promising agents for treating melanoma. Given that autoimmune skin diseases exhibit hyper immune reaction, investigation of immune cells from autoimmune skin disease is crucial to validate the effectiveness of ICIs in melanoma treatment. We employed multipanel markers to predict the response to immune checkpoint inhibitors by characterizing the gene expression signatures of skin immune cells in systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis (PS). By analyzing single-cell RNA sequencing data from each dataset, T cell gene signatures from autoimmune skin diseases exhibit a complex immune response in tumors that responded to immunotherapy. Based on that CD86 and CD80 provide essential costimulatory signals for T cell activation, we observed that interaction of CD86 signaling has been enhanced in the T cells of patients with SLE, AD, and PS. Our analysis revealed a common increase in CD86 signals from dendritic cells (DCs) to T cells in patients with SLE, AD, and PS, confirming that dendritic cells produce pro-inflammatory cytokines to activate T cells. Thus, we hypothesize that T cell gene signatures from autoimmune skin diseases exhibit a pro-inflammatory response and have the potential to predict cancer immunotherapy. Our study demonstrated that T cell gene signatures derived from inflammatory skin diseases, particularly SLE and PS, hold promise as potential biomarkers for predicting the response to immune checkpoint blockade therapy in patients with melanoma. Our data provide an understanding of the immune-related characteristics and differential gene expression patterns in autoimmune skin diseases, which may represent promising targets for melanoma immunotherapy.

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“…Specifically, we observed a standard increase in CD86 signals from myeloid cells to T cells in the SLE, AD, and PS datasets 28 , 29 (Fig. 3 B).…”

Section: Resultsmentioning

confidence: 79%

Gene signature from cutaneous autoimmune diseases provides potential immunotherapy-relevant biomarkers in melanoma

Chun,

Park,

Hwang

et al. 2023

Sci Rep

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“…As FE concentration increased, the proportion of differentiated Th2 cells decreased significantly (Figures 6D, E). We hypothesized that is the result of inhibition of the JAK-STAT3/6-GATA3 pathway after the reduction of IL-4 and IL-13, thereby regulating T cell proliferation and Th2 cell differentiation (Gandhi et al, 2016;Zheng et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Cell-free fat extract regulates oxidative stress and alleviates Th2-mediated inflammation in atopic dermatitis

Fu,

Gu,

Wang

et al. 2024

Front. Bioeng. Biotechnol.

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Atopic dermatitis (AD) is a common inflammatory skin disease that significantly affects patients’ quality of life. This study aimed to evaluate the therapeutic potential of cell-free fat extract (FE) in AD. In this study, the therapeutic effect of DNCB-induced AD mouse models was investigated. Dermatitis scores and transepidermal water loss (TEWL) were recorded to evaluate the severity of dermatitis. Histological analysis and cytokines measurement were conducted to assess the therapeutic effect. Additionally, the ability of FE to protect cells from ROS-induced damage and its ROS scavenging capacity both in vitro and in vivo were investigated. Furthermore, we performed Th1/2 cell differentiation with and without FE to elucidate the underlying therapeutic mechanism. FE reduced apoptosis and cell death of HaCat cells exposed to oxidative stress. Moreover, FE exhibited concentration-dependent antioxidant activity and scavenged ROS both in vitro and vivo. Treatment with FE alleviated AD symptoms in mice, as evidenced by improved TEWL, restored epidermis thickness, reduced mast cell infiltration, decreased DNA oxidative damage and lower inflammatory cytokines like IFN-γ, IL-4, and IL-13. FE also inhibited the differentiation of Th2 cells in vitro. Our findings indicate that FE regulates oxidative stress and mitigates Th2-mediated inflammation in atopic dermatitis by inhibiting Th2 cell differentiation, suggesting that FE has the potential as a future treatment option for AD.

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“…OX40 binds to its endogenous ligand, OX40L, which can be induced on activated B cells, mature conventional dendritic cells (cDCs), plasmacytoid dendritic cells (pDCs), Langerhans cells, and macrophages in response to factors that promote antigen-presenting cell (APC) activation and maturation [27][28][29][30][31]. OX40L expression primarily occurs on professional APCs [11,32,33]. OX40L may also be expressed on type 2 innate lymphoid cells (ILC2s) and non-lymphoid cells, including endothelial cells, fibroblasts, smooth muscle cells, and mast cells [26,[34][35][36].…”

Section: Ox40l Expressionmentioning

confidence: 99%

“…IL-4 and IL-13 are proinflammatory cytokines secreted by T H 2 cells that downregulate filaggrin, loricrin, and involucrin production in the epidermis [9,74]. The downregulation of these structural proteins compromises skin barrier integrity [23,33,57]. The subsequent disturbance of the epidermal barrier establishes a feedback loop that increases TSLP production and stimulates OX40L expression, thus contributing to the T H 2 cell predominance that characterizes early-stage AD [3].…”

Section: T Helper 2 Cellsmentioning

confidence: 99%

An OX-Tra’Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis

Sadrolashrafi,

Guo,

Kikuchi

et al. 2024

Cells

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The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management.

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T cell co-stimulatory and co-inhibitory pathways in atopic dermatitis

Cited by 10 publications

References 245 publications

Gene signature from cutaneous autoimmune diseases provides potential immunotherapy-relevant biomarkers in melanoma

Gene signature from cutaneous autoimmune diseases provides potential immunotherapy-relevant biomarkers in melanoma

Cell-free fat extract regulates oxidative stress and alleviates Th2-mediated inflammation in atopic dermatitis

An OX-Tra’Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis

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