更新于：2024-05-01
CCL4
趋化因子CCL4
更新于：2024-05-01
基本信息
别名 ACT-2、AT744.1、C-C motif chemokine 4 + [20] |
简介 Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B. |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
A Phase 1, Open-Label, Multicenter, Dose Escalation and Expansion Study of ONCR-177, an Oncolytic Herpes Simplex Virus for Intratumoral Injection, Alone and in Combination With PD-1 Blockade in Adult Subjects With Advanced and/or Refractory Cutaneous, Subcutaneous or Metastatic Nodal Solid Tumors or With Liver Metastases of Solid Tumors
100 项与 CCL4 相关的临床结果
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100 项与 CCL4 相关的转化医学
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2024-02-19Computers in biology and medicine
Integrated analysis of single-cell and bulk RNA sequencing data reveals the association between hypoxic tumor cells and exhausted T cells in predicting immune therapy response.
Article
作者: Min Yan ; Ruixin Wu ; Han Fu ; Chao Hu ; Yanan Hao ; Jie Zeng ; Tong Chen ; Yingming Wang ; Yingying Wang ; Jing Hu ; Aishun Jin
Continuous stimulation of tumor neoantigens and various cytokines in the tumor microenvironment leads to T cell dysfunction, but the specific mechanisms by which these key factors are distributed among different cell subpopulations and how they affect patient outcomes and treatment response are incompletely characterized. By integrating single-cell and bulk sequencing data of non-small cell lung cancer patients, we constructed a clinical outcome-associated T cell exhaustion signature. We discovered a significant association between the T cell exhaustion state and tumor cell hypoxia. Hypoxic malignant cells were significantly correlated with the proportion of exhausted T cells, and they co-occurred in patients at advanced stage. By analyzing the ligand-receptor interactions between these two cell states, we observed that T cells were recruited towards tumor cells through production of chemokines such as CXCL16-CXCR6 axis and CCL3/CCL4/CCL5-CCR5 axis. Based on 15 immune checkpoint blockade (ICB)-treatment cohorts, we constructed an interaction signature that can be used to predict the response to immune checkpoint blockade therapy. Among genes composed of the signature, CXCR6 alone has similarly high prediction efficacy (Area Under Curve (AUC) = 1, 0.89 and 0.73 for GSE126044, GSE135222 and GSE93157, respectively) with the signature and thus could serve as a potential biomarker for predicting immunotherapy response. Together, we have discovered and validated a significant association between exhausted T cells and hypoxic malignant cells, elucidating key interaction factors that significantly associated with response to immunotherapy.
2024-02-16Journal of leukocyte biology
6-Formylindolo[3,2-b]carbazole, a potent ligand for the aryl hydrocarbon receptor, attenuates concanavalin-induced hepatitis by limiting T-cell activation and infiltration of proinflammatory CD11b+ Kupffer cells.
Article
作者: Alkeiver S Cannon ; Bryan L Holloman ; Kiesha Wilson ; Kathryn Miranda ; Prakash S Nagarkatti ; Mitzi Nagarkatti
FICZ (6-formylindolo[3,2-b]carbazole) is a potent aryl hydrocarbon receptor agonist that has a poorly understood function in the regulation of inflammation. In this study, we investigated the effect of aryl hydrocarbon receptor activation by FICZ in a murine model of autoimmune hepatitis induced by concanavalin A. High-throughput sequencing techniques such as single-cell RNA sequencing and assay for transposase accessible chromatin sequencing were used to explore the mechanisms through which FICZ induces its effects. FICZ treatment attenuated concanavalin A-induced hepatitis, evidenced by decreased T-cell infiltration, decreased circulating alanine transaminase levels, and suppression of proinflammatory cytokines. Concanavalin A revealed an increase in natural killer T cells, T cells, and mature B cells upon concanavalin A injection while FICZ treatment reversed the presence of these subsets. Surprisingly, concanavalin A depleted a subset of CD55+ B cells, while FICZ partially protected this subset. The immune cells showed significant dysregulation in the gene expression profiles, including diverse expression of migratory markers such as CCL4, CCL5, and CXCL2 and critical regulatory markers such as Junb. Assay for transposase accessible chromatin sequencing showed more accessible chromatin in the CD3e promoter in the concanavalin A-only group as compared to the naive and concanavalin A-exposed, FICZ-treated group. While there was overall more accessible chromatin of the Adgre1 (F4/80) promoter in the FICZ-treated group, we observed less open chromatin in the Itgam (CD11b) promoter in Kupffer cells, supporting the ability of FICZ to reduce the infiltration of proinflammatory cytokine producing CD11b+ Kupffer cells. Taken together, these data demonstrate that aryl hydrocarbon receptor activation by FICZ suppresses liver injury through the limitation of CD3+ T-cell activation and CD11b+ Kupffer cell infiltration.
2024-02-15Experimental neurology
Social isolation initiated post-weaning augments ischemic brain injury by promoting pro-inflammatory responses.
Article
作者: Muhammed Furkan Dasdelen ; Ahmet Burak Caglayan ; Sezgin Er ; Mustafa Caglar Beker ; Nilay Ates ; Janine Gronewold ; Thorsten Roland Doeppner ; Dirk M Hermann ; Ertugrul Kilic
Social isolation is associated with poor stroke outcome, but the underlying molecular mechanisms were largely unknown. In male Balb/C mice exposed to transient middle cerebral artery occlusion (MCAo), we examined the effects of social isolation initiated post-weaning on ischemic injury, cytokine/chemokine responses and cell signaling using a broad panel of techniques that involved immunocytochemistry, cytokine/chemokine array and Western blots. Social isolation initiated post-weaning elevated infarct size, brain edema and neuronal injury in the ischemic brain tissue 3 days after MCAo, and increased microglia/ macrophage and leukocyte accumulation. In line with the increased immune cell recruitment, levels of several proinflammatory cytokines (e.g., IL-1α, IL-1β, IL-13, IL-17, TNF-α, IFN-γ), chemokines (e.g., CCL3, CCL4, CCL12, CXCL2, CXCL9, CXCL12) and adhesion molecules (i.e., ICAM-1) were increased in the ischemic brain tissue of socially isolated compared with paired housing mice, whereas levels of selected cytokines (IL-5, IL-6, IL-16) and colony-stimulating factors (G-CSF, GM-CSF) were reduced. The activity of the transcription factor nuclear factor-ĸB (NF-ĸB), which promotes cell injury via pro-inflammatory responses, was increased by social isolation, whereas that of nuclear factor erythroid related factor-2 (Nrf-2), which mediates anti-oxidative responses under oxidative stress conditions, was reduced. Our study shows that social isolation profoundly alters post-ischemic cell signaling in a way promoting pro-inflammatory responses. Our results highlight the importance of social support in preventing deleterious health effects of social isolation.
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