Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens

Flores-Mendoza, Giovanna; Rodríguez-Rodríguez, Noé; Rubio, Rosa M; Madera-Salcedo, Iris K.; Rosetti, Florencia; Crispín, José C.

doi:10.3389/fimmu.2021.635862

Cited by 11 publications

(8 citation statements)

References 57 publications

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“…[ 30 ] FASLG expression is upregulated in CD8 + T‐cells during cell activation. [ 31 ] FASLG inhibits normal hematopoiesis in myelodysplastic syndrome marrow. [ 32 ] Our results support the notion that FAS‐FALG signaling is a therapeutic target for AA.…”

Section: Discussionmentioning

confidence: 99%

Unbiased Single‐Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation

Guo,

Kong,

Tang

et al. 2023

Advanced Science

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Aplastic anemia (AA) is a bone marrow (BM) failure syndrome mediated by hyperactivated T‐cells with heterogeneous pathogenic factors. The onset of BM failure cannot be accurately determined in humans; therefore, exact pathogenesis remains unclear. In this study, a cellular atlas and microenvironment interactions is established using unbiased single‐cell RNA‐seq, along with multi‐omics analyses (mass cytometry, cytokine profiling, and oxidized fatty acid metabolomics). A new KIR+CD8+ regulatory T cells (Treg) subset is identified in patients with AA that engages in immune homeostasis. Conventional CD4+ T‐cells differentiate into highly differentiated T helper cells with type 2 cytokines (IL‐4, IL‐6, and IL‐13), GM‐SCF, and IL‐1β. Immunosuppressive homeostasis is impaired by enhanced apoptosis of activated Treg cells. Pathological Vδ1 cells dominated the main fraction of γδ T‐cells. The B/plasma, erythroid, and myeloid lineages also exhibit substantial pathological features. Interactions between TNFSF12‐TNFRSF12A, TNF‐TNFRSF1A, and granzyme‐gasdermin are associated with the cell death of hematopoietic stem/progenitor (HSPCs), Treg, and early erythroid cells. Ferroptosis, a major driver of HSPCs destruction, is identified in patients with AA. Furthermore, a case of twins with AA is reported to enhance the persuasiveness of the analysis. These results collectively constitute the cellular atlas and microenvironment interactions in patients with AA and provide novel insights into the development of new therapeutic opportunities.

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Section: Discussionmentioning

confidence: 99%

Unbiased Single‐Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation

Guo,

Kong,

Tang

et al. 2023

Advanced Science

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“…As the disease progresses, the proportion of tissue-resident memory T cells gradually increases, probably because they are better able to localize and function in the pancreas. Therefore, the changes in the proportions of T eff , T cm and T scm cells, as well as T rm cells, in T1D are dynamic and may be influenced by a variety of factors (67). The environment of early naive T cells can change the activation state of CD8+ T cells, leading to memory T cells, exhausted T cells, senescent T cells, and so on.…”

Section: Autoimmune Cd8+ T Cells In T1dmentioning

confidence: 99%

“…One of them is CD8 memory T cells. An initial expanded vaccination regimen can result in multiple contacts with Ag over the host's lifetime due to recurrent exposure to the same pathogen, which increases the amount of CD8 memory T cells (67,71). Effector CD8+ cells are another state.…”

Section: Autoimmune Cd8+ T Cells In T1dmentioning

confidence: 99%

Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection

Yang,

Zhang,

Ding

et al. 2024

Front. Endocrinol.

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Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic β cell destruction and mediated primarily by autoreactive CD8+ T cells. It has been shown that only a small number of stem cell-like β cell-specific CD8+ T cells are needed to convert normal mice into T1D mice; thus, it is likely that T1D can be cured or significantly improved by modulating or altering self-reactive CD8+ T cells. However, stem cell-type, effector and exhausted CD8+ T cells play intricate and important roles in T1D. The highly diverse T-cell receptors (TCRs) also make precise and stable targeted therapy more difficult. Therefore, this review will investigate the mechanisms of autoimmune CD8+ T cells and TCRs in T1D, as well as the related single-cell RNA sequencing (ScRNA-Seq), CRISPR/Cas9, chimeric antigen receptor T-cell (CAR-T) and T-cell receptor-gene engineered T cells (TCR-T), for a detailed and clear overview. This review highlights that targeting CD8+ T cells and their TCRs may be a potential strategy for predicting or treating T1D.

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“…In addition to directly regulating T cell function, VEGF also can suppress T cell function by regulating Fas ligand (FasL) levels, which is upregulated by VEGF-A in the TME [52,53]. FasL is expressed on the surface of T cells and in tumor endothelium; however, it is not seen in a normal vascular system [48,54].…”

Section: Vegf and T Cellsmentioning

confidence: 99%

VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment

Zhao¹,

Guo²,

Deng³

et al. 2022

Int. J. Biol. Sci.

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Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC.

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Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens

Cited by 11 publications

References 57 publications

Unbiased Single‐Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation

Unbiased Single‐Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation

Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection

VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment

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