Ask about this productRelated genes to: CCR5 antibody
- Gene:
- CCR5 NIH gene
- Name:
- C-C motif chemokine receptor 5 (gene/pseudogene)
- Previous symbol:
- CMKBR5
- Synonyms:
- CKR-5, CC-CKR-5, CKR5, CD195, IDDM22
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 1996-05-15
- Date modifiied:
- 2019-01-10
Related products to: CCR5 antibody
Related articles to: CCR5 antibody
- Myocardial ischemia-reperfusion injury (MIRI) remains a major clinical challenge due to limited therapeutic options and the risk of complications such as hemorrhage. Dihydromyricetin (DMY), a flavonoid derived from Vine tea, has shown cardioprotective effects, but its mechanism of action in MIRI is not fully understood. This study aimed to investigate the therapeutic effects of DMY on MIRI and elucidate the underlying molecular mechanisms. A rat model of MIRI was established by left anterior descending coronary artery ligation. Rats received DMY or the positive control diltiazem (DIL) for 7 days post-injury. Cardiac damage was assessed by measuring cardiac troponin levels and histopathological analysis. The expression of chemokine-like factor 1 (CKLF1) and its downstream signaling pathways was examined using molecular and biochemical approaches. The interaction between DMY and CKLF1 was further validated using a CKLF1 agonist (C27) and CKLF1-knockout rats. CKLF1 expression was significantly upregulated in MIRI, correlating with inflammatory infiltration, tissue disorganization, and elevated cardiac troponin levels. Mechanistically, CKLF1 activation promoted phosphorylation of nuclear factor kappa-B (NF-κB) and subsequent assembly of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, leading to caspase-1-dependent pyroptosis. DMY treatment attenuated these effects by downregulating CKLF1 expression and disrupting its interaction with C-C chemokine receptor type 5 (CCR5) and NLRP3, thereby suppressing pyroptosis. Notably, activation of CKLF1 signaling by its agonist C27 reversed the protective effects of DMY. Moreover, while CKLF1 knockout modestly reduced pyroptosis-related protein expression, the anti-pyroptotic effect of DMY was abolished in knockout rats, indicating its dependence on CKLF1. These findings demonstrate that DMY alleviates MIRI by targeting the CKLF1/NF-κB/NLRP3 axis, thereby inhibiting pyroptosis and preserving cardiomyocyte integrity. The anti-pyroptotic effect of DMY is specifically dependent on CKLF1 expression. This study provides a novel mechanistic basis for developing targeted therapies against MIRI. - Source: PubMed
Publication date: 2026/05/29
Lin YutingSun YangLiang JinpingChen ChenYan QianLong JunpengWang HanlongZhang ZhunhongLi PeiyiQu ShanheYu JingboGao YanWang HuiqinYang SongweiLin MeiyuLiu XuanYao JiaoTian ZhifengChen NaihongYang YantaoLiu ShashaAi Qidi - Atherosclerosis is a leading cause of global morbidity and mortality. Cholesterol crystal embolism (CCE) in advanced atherosclerosis can lead to acute kidney injury (AKI) through ischemic cortical necrosis. However, a single-cell atlas of the CCE kidney remains incomplete, impeding rational therapeutic design. In a C57BL/6J mouse CCE model generated by unilateral renal artery CC injection, single-cell transcriptomics revealed widespread changes across 17 kidney cell types. The differentially expressed genes (DEGs) varied markedly, with 1659 in the ascending loop of Henle and 1505 in proximal tubules, whereas only 7 were in dendritic cells. Cell-cell interaction analyses revealed a central role for C-C motif chemokine ligand (CCL)-C-C motif chemokine receptor 5 (CCR5) and macrophage migration inhibitory factor (MIF)-cluster of differentiation 74 (CD74) pathways in CCE formation and related outcomes, including vascular injury, AKI, and immune cell infiltration. Human kidney biopsies from patients with CCE showed CD74-positive staining near obstructed arteries with cholesterol clefts. Pharmacological inhibition of CCR5 or CD74 using maraviroc or milatuzumab, respectively, as well as their combined administration before CC injection, reduced vascular thrombosis and tissue damage without raising bleeding risk in the C57BL/6J mouse CCE model. Even when treatment was delayed by 2 hours postembolism, it still decreased complications like thrombotic angiopathy and AKI upon CCE. These findings highlight CCR5 and CD74 as potential therapeutic targets for CCE-related necroinflammation. - Source: PubMed
Publication date: 2026/05/27
Shi ChongxuWen ZhaozhiZheng KoulongLi BowenMiao HuipingKlinkhammer Barbara MBoor PeterAnders Hans-JoachimLiu Dong - Head and neck squamous cell carcinoma (HNSCC) frequently resists PD-1 blockade due to an immunologically "cold" tumor microenvironment (TME). Here, we identify Z-DNA binding protein 1 (ZBP1) as a key immunoregulator that reprograms immune-suppressive TMEs. Integrated TCGA/SangerBox analyses revealed ZBP1 as a hub gene strongly correlated with cytotoxic CD8+ T cells (r = 0.48, p < 0.0001) and M1 macrophages (r = 0.39, p < 0.0001). Multi-model validation in 92 HNSCC specimens revealed elevated ZBP1 expression versus normal tissues (p < 0.01), co-localized with infiltrating CD8+/CD4+ T cells and CD68+ macrophages through multiplex immunofluorescence. Clinically, high ZBP1 predicted improved survival (HR = 0.61 for overall survival; HR = 0.45 for disease specific survival; p < 0.0001) and early-stage presentation (p = 0.004). Mechanistically, ZBP1 overexpression in SCC-7/MOC2 models suppressed tumor growth while enhancing IFN-γ+ CD8+ T cell activation and reducing M2 polarization (CD206+: 16.91% vs 38.19% in ZBP1-high vs control, p < 0.001). Single-cell transcriptomics uncovered ZBP1-driven TME remodeling through chemokine signaling networks and expanded effector T cell compartments, validated by 1.49-fold increased CD8+ T cell infiltration via flow cytometry. Spatial analysis revealed ZBP1 overexpression amplified immune cell crosstalk (1.65-fold interaction increase, p < 0.001), upregulating CD8+ T cell chemotaxis (CXCR3/CCR5-CCL5 axis) and effector functions (p < 0.0001). Concurrently, it suppressed immunosuppressive pathways (ARG1 ↓ /IDO1↓) through metabolic reprogramming, establishing ZBP1 as a dual regulator synchronizing lymphocyte recruitment and myeloid suppression. Our integrative approach bridges computational biology with functional validation, demonstrating ZBP1's capacity to convert "cold" tumors into immunologically active niches. This work positions ZBP1 as both a stratification biomarker for checkpoint inhibitor response and a therapeutic target for TME reprogramming in HNSCC. - Source: PubMed
Publication date: 2026/05/26
Min YuSong GeYang LianlianHe LingXu ShihongGao KunLiu ZheranPeng XingchenDai Lei - Despite prolonged viral inhibition with combination antiretroviral therapy (ART), HIV-1 survives as genetically intact, replication-capable proviruses within durable CD4+ T-cell fractions, involving central memory, transitional memory, and stem cell-like memory populations, as well as within tissue-resident compartments including lymphoid follicles and gut-associated lymphoid tissue. Reservoir stability is preserved via clonal growth of infected cells and epigenetic processes that impose proviral transcriptional silencing. As a result, current therapeutic approaches seek to either directly alter proviral survival or to improve immune-driven elimination of infected cells. At the molecular level, investigational strategies such as CRISPR-Cas9 and CRISPR-Cas12 gene-editing systems are intended to remove or induce inactivating mutations inside embedded proviral DNA, as well as alter host entrance co-receptors such as CCR5 to provide cellular resistance to infection. In addition, pharmacologic latency regulation is being studied via histone deacetylase inhibitors, protein kinase C agonists, and bromodomain inhibitors to reverse latency, along with Tat inhibitors and other transcriptional repressors aimed to persistently silence proviral expression. Moreover, immunological techniques aim to counteract inefficient endogenous antiviral defenses. Broadly neutralizing antibodies with tailored Fc-driven effector functions are under examination for both neutralization and antibody-dependent cellular cytotoxicity. Therapeutic vaccine approaches seek to elevate polyfunctional HIV-specific CD8+ T-cell responses, while adoptive cellular approaches, involving CAR-T cells aiming HIV envelope epitopes, remain in early clinical research. Immune checkpoint blockade is also being investigated to reverse T-cell depletion inside reservoir-rich tissues. Nevertheless, the key obstacles continue to be the diverse reservoir composition, restricted tissue penetration, viral escape, and safety limitations. The molecular and translational obstacles that characterize attempts toward an HIV cure must be addressed through ongoing multidisciplinary research. - Source: PubMed
Publication date: 2026/04/26
Alanazi AwadhIbrahim Mohamed NElithy Mohamed A - Specific anaerobic species within the penile microbiome - Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) - have been linked to increased HIV-1 susceptibility. These bacteria can directly disrupt epithelial integrity and are believed to increase local inflammation, resulting in an increased density of HIV-susceptible T cells in the inner foreskin. It is currently unknown whether other immune cells bearing the HIV entry receptors, CD4 and CCR5, are also elevated in individuals with a high abundance of BASIC species. Using inner foreskin tissues and penile swabs from males undergoing voluntary medical male circumcision, we performed a retrospective cross-sectional study to assess the relationship between BASIC species and the tissue density of such immune cells, including CD68+ macrophages, CD11c+ dendritic cells, and CD207+ Langerhans cells. The most abundant cells in the inner foreskin expressing the HIV co-receptors were CD11c+ dendritic cells (48.6% of CD4+/CCR5+ cells), followed by CD68+ macrophages (28.6%), CD3+ T cells (18.8%), and CD207+ Langerhans-like (8.8%) cells. The absolute abundance of BASIC species was associated with elevated tissue densities of both CD4+/CCR5+ T cells (as previously reported) and a heterogeneous population of CD3-/CD4+/CCR5+ cells of myeloid origin. In the dermis, BASIC species abundance was linked to elevated densities of cells expressing CD11c, CD68, and CD207, as well as those co-expressing CD11c and CD207; furthermore, CD11c+ and CD207+ cells were farther from the basement membrane in participants with a high abundance of BASIC species. Myeloid cells were not elevated in participants with a high abundance of control taxa. In an integrated analysis including previously published data from this same cohort, myeloid-cell densities clustered tightly together, positively correlated with BASIC species and pro-inflammatory cytokines, and had trends to negative correlations with control taxa (significant for CD207+ cell density). Overall, our findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible myeloid and T cells, alongside epithelial disruption. - Source: PubMed
Publication date: 2026/05/14
Buchanan Lane BKhan YazanVargas Jorge RShao ZhongtianBiribawa Victoria MenyaSsemunywa Henry RogersNamuniina AnnemarieOkech BrendaTobian Aaron ArPark Daniel ELiu Cindy MKaul RupertGaliwango Ronald MProdger Jessica L