Topic
CCR4
About: CCR4 is a research topic. Over the lifetime, 285 publications have been published within this topic receiving 18225 citations. The topic is also known as: C-C chemokine receptor type 4 & chemokine (C-C) receptor 4.
Papers published on a yearly basis
Papers
TL;DR: The in vitro migration capacity of human BM‐derived MSCs, preincubated or not with the inflammatory cytokines interleukin 1β (IL1β) and tumor necrosis factor α (TNFα), in response to 16 growth factors and chemokines is compared.
Abstract: Adult bone marrow (BM)-derived stem cells, including hematopoietic stem cells (HSCs) and MSCs, represent an important source of cells for the repair of a number of damaged tissues. In contrast to HSCs, the soluble factors able to induce MSC migration have not been extensively studied. In the present work, we compared the in vitro migration capacity of human BM-derived MSCs, preincubated or not with the inflammatory cytokines interleukin 1beta (IL1beta) and tumor necrosis factor alpha (TNFalpha), in response to 16 growth factors (GFs) and chemokines. We show that BM MSCs migrate in response to many chemotactic factors. The GFs platelet-derived growth factor-AB (PDGF-AB) and insulin-like growth factor 1 (IGF-1) are the most potent, whereas the chemokines RANTES, macrophage-derived chemokine (MDC), and stromal-derived factor-1 (SDF-1) have limited effect. Remarkably, preincubation with TNFalpha leads to increased MSC migration toward chemokines, whereas migration toward most GFs is unchanged. Consistent with these results, BM MSCs express the tyrosine kinase receptors PDGF-receptor (R) alpha, PDGF-Rbeta, and IGF-R, as well as the RANTES and MDC receptors CCR2, CCR3, and CCR4 and the SDF-1 receptor CXCR4. TNFalpha increases CCR2, CCR3, and CCR4 expression (as opposed to that of CXCR4), together with RANTES membrane binding. These data indicate that the migration capacity of BM MSCs is under the control of a large range of receptor tyrosine kinase GFs and CC and CXC chemokines. Most chemokines are more effective on TNFalpha-primed cells. Our results suggest that the mobilization of MSCs and their subsequent homing to injured tissues may depend on the systemic and local inflammatory state. Disclosure of potential conflicts of interest is found at the end of this article.
1,009 citations
TL;DR: Findings provide a rationale for the use of agents that block CCR5 and/or CXCR3 as a therapeutic approach in the treatment of MS and potentially for other chronic autoimmune/inflammatory processes such as rheumatoid arthritis, autoimmune diabetes, or chronic transplant rejection.
Abstract: Multiple sclerosis (MS) is a T cell-dependent chronic inflammatory disease of the central nervous system. The role of chemokines in MS and its different stages is uncertain. Recent data suggest a bias in expression of chemokine receptors by Th1 vs. Th2 cells; human Th1 clones express CXCR3 and CCR5 and Th2 clones express CCR3 and CCR4. Chemokine receptors expressed by Th1 cells may be important in MS, as increased interferon-γ (IFN-γ) precedes clinical attacks, and IFN-γ injection induces disease exacerbations. We found CXCR3+ T cells increased in blood of relapsing-remitting MS, and both CCR5+ and CXCR3+ T cells increased in progressive MS compared with controls. Furthermore, peripheral blood CCR5+ T cells secreted high levels of IFN-γ. In the brain, the CCR5 ligand, MIP-1α, was strongly associated with microglia/macrophages, and the CXCR3 ligand, IP-10, was expressed by astrocytes in MS lesions but not unaffected white matter of control or MS subjects. Areas of plaque formation were infiltrated by CCR5-expressing and, to a lesser extent, CXCR3-expressing cells; Interleukin (IL)-18 and IFN-γ were expressed in demyelinating lesions. No leukocyte expression of CCR3, CCR4, or six other chemokines, or anti-inflammatory cytokines IL-5, IL-10, IL-13, and transforming growth factor-β was observed. Thus, chemokine receptor expression may be used for immunologic staging of MS and potentially for other chronic autoimmune/inflammatory processes such as rheumatoid arthritis, autoimmune diabetes, or chronic transplant rejection. Furthermore, these results provide a rationale for the use of agents that block CCR5 and/or CXCR3 as a therapeutic approach in the treatment of MS.
898 citations
TL;DR: The data implicate TSLP, TARC/ CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis, which may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.
Abstract: Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p
866 citations
TL;DR: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD.
Abstract: Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T H 2-type cells in lesional skin Thymus and activation-regulated chemokine (TARC/CCL17) is a chemokine that attracts CC chemokine receptor 4–positive (CCR4 + ) or CCR8 + cells Objective: The purpose of this study was to investigate the participation of TARC in AD Methods: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors The positivity of CCR4 of CD4 + CD45RO + cells in PBMCs was examined by using FACS analysis Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD Results: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis The serum TARC levels significantly correlated with eosinophil number ( r = 061), SCORAD score ( r = 060), and serum soluble E-selectin levels ( r = 058) and weakly correlated with serum soluble IL-2 receptor levels ( r = 034) in patients with AD The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms The CCR4 positivity of CD4 + CD45RO + cells in PBMCs of patients with AD was also higher than that of healthy control subjects Immunohistochemical staining revealed that TARC was positive in ke-ratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis Conclusion: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD (J Allergy Clin Immunol 2001;107:535-41)
568 citations
TL;DR: Evidence is provided that chemokines and gp120 may produce painful effects via direct actions on chemokine receptors expressed by nociceptive neurons in rats associated with HIV-1 infection and inflammation.
Abstract: Human immunodeficiency virus-1 (HIV-1) infection is associated with numerous effects on the nervous system, including pain and peripheral neuropathies. We now demonstrate that cultured rat dorsal root ganglion (DRG) neurons express a wide variety of chemokine receptors, including those that are thought to act as receptors for the HIV-1 coat protein glycoprotein120 (gp120). Chemokines that activate all of the known chemokine receptors increased [Ca2+]iin subsets of cultured DRG cells. Many neurons responded to multiple chemokines and also to bradykinin, ATP, and capsaicin. Immunohistochemical studies demonstrated the expression of the CXCR4 and CCR4 chemokine receptors on populations of DRG neurons that also expressed substance P and the VR1 vanilloid receptor. RT-PCR analysis confirmed the expression of CXCR4, CX3CR1, CCR4, and CCR5 mRNAs in DRG neurons. Chemokines and gp120 produced excitatory effects on DRG neurons and also stimulated the release of substance P. Chemokines and gp120 also produced allodynia after injection into the rat paw. Thus these results provide evidence that chemokines and gp120 may produce painful effects via direct actions on chemokine receptors expressed by nociceptive neurons. Chemokine receptor antagonists may be important therapeutic interventions in the pain that is associated with HIV-1 infection and inflammation.
479 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 4 |
| 2024 | 23 |
| 2023 | 86 |
| 2022 | 40 |
| 2021 | 13 |
| 2020 | 13 |