IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression

Stein, Stephanie; Henze, Lara; Poch, T; Carambia, Antonella; Krech, Till; Preti, Max; Schuran, Fenja Amrei; Reich, Maria; Keitel, Verena; Fiorotto, Romina; Strazzabosco, Mario; Fischer, Lutz; Li, Jun; Müller, Luisa; Wagner, Jonas; Gagliani, Nicola; Herkel, Johannes; Schwinge, Dorothee; Schramm, Christoph

doi:10.1016/j.jhep.2020.10.035

Cited by 26 publications

(24 citation statements)

References 52 publications

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“…IL-17 is therefore implicated as a novel instigator in the pro-inflammatory microglia activation. IL-17, a pleiotropic cytokine, influences many kinds of cells biology in the context of disease (Sigurdardottir et al, 2019;Stein et al, 2021;Talia et al, 2016). Previous studies have reported the IL-17-dependent activities in immune cells like B cells and macrophages, as well as nonimmune cells such as synoviocytes, epithelial cells, and keratinocytes (Cua & Tato, 2010).…”

Section: Discussionmentioning

confidence: 99%

IL‐17 signaling induces iNOS+ microglia activation in retinal vascular diseases

Zhou

Liang

Yang

et al. 2021

Glia

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Activation of microglia and inflammation-mediated vascular damages are suggested to play a decisive role in the pathogenesis of various retinopathies. The inducible nitric oxide synthase (iNOS) was required for activated microglia-mediated injuries.However, the induction mechanism of microglia activation during retinal vascular diseases is still elusive. Here we showed that IL-17 induced microglia activation with high expression of iNOS and promoted the development of retinal vascular diseases.

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Section: Discussionmentioning

confidence: 99%

IL‐17 signaling induces iNOS+ microglia activation in retinal vascular diseases

Zhou

Liang

Yang

et al. 2021

Glia

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“…Several studies have shown that IFN-γ can induce PD-L1 expression through the IFN-γ/JAK/STAT1 signaling pathway, thereby promoting the immune escape of cancer cells [ 101 , 102 ]. In addition to IFN-γ, several other inflammatory cytokines also enhance PD-L1 expression on cancer cells or tumor-associated stromal cells, such as IFN-α/β [ 66 ], Toll-like receptors3/4 [ 63 , 73 ], TNF-α [ 103 ], TGF-β [ 104 ], and IL-4/6/10/17/27 [ 64 , 65 , 71 , 72 , 105 ]. Interestingly, the detection of the expression of inflammatory cytokines (e.g., IFN-γ, TNF-α, and several ILs) is a predictor of immune checkpoint therapy outcome for advanced NSCLC, while high expression of inflammatory cytokines is positively correlated with anti-PD-1 therapeutic effectiveness [ 106 ].…”

Section: The Role Of Pd-l1 In Tumor Immune Escapementioning

confidence: 99%

Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

et al. 2022

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Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8+ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets.

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“…In these cases, ursodeoxycholic acid (UDCA) improved liver tests. This hypothesis is supported by the in vitro data regarding PD-1 blockers and an increased risk of cholangitis ( Stein et al, 2021 ). Future work should be conducted to determine the place of UDCA in the management of ICI-induced liver injury.…”

Section: Immune Checkpoint Inhibitor-induced Liver Toxicitymentioning

confidence: 64%

Immunotherapy and Gene Therapy: New Challenges in the Diagnosis and Management of Drug-Induced Liver Injury

et al. 2022

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In the last 5 years, the landscape of oncologic treatment has been deeply modified with the development and use of immune checkpoint inhibitors (ICIs) that exert their antitumoral effect by reverting the exhausted phenotype of tumor-infiltrating lymphocytes. This innovative therapeutic strategy has widely changed the prognosis of some advanced neoplastic diseases such as melanoma and lung cancer, providing durable remission for a significant number of patients. Unfortunately, immune-related adverse events (irAEs), especially ICI-induced hepatitis, may be very severe in some cases, impairing the prognosis of the patient. Guidelines available today on the diagnosis and management of ICI-induced hepatitis are mainly based on expert opinions and case series. This lack of large data is explained not only by the low incidence of hepatic adverse events but also by their clinical heterogeneity and variable severity. In this article, we will review the clinical, biological, and histological characteristics of ICI-induced liver injury. We will discuss the current knowledge on their pathological mechanisms and their therapeutic strategy based on immunosuppressive treatment for more severe cases. Regarding severity assessment, we will discuss the gap between the oncologist and the hepatologist’s point of view, highlighting the need for multidisciplinary management. While initially developed for notably less frequent diseases than neoplastic ones, gene therapy is going to be a revolution for the treatment of diseases not responding to pharmacological therapy. Limited but growing data describe liver injury after the administration of such therapy whose exact physiopathology remains unknown. In this article, we will discuss the available data supporting the role of gene therapies in the onset of drug-induced liver injury and related mechanisms. We will describe the clinical context, the biological and histological features, and the management currently proposed.

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IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression

Cited by 26 publications

References 52 publications

IL‐17 signaling induces iNOS+ microglia activation in retinal vascular diseases

IL‐17 signaling induces iNOS+ microglia activation in retinal vascular diseases

Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

Immunotherapy and Gene Therapy: New Challenges in the Diagnosis and Management of Drug-Induced Liver Injury

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