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At least 19 recordsLinked to original sources
PubMed2004

ATP priming of macrophage-derived chemokine responses in CHO cells expressing the CCR4 receptor.

The mechanism by which ATP primes for subsequent macrophage-derived chemokine (MDC) mediated intracellular calcium (Ca2+(i)) responses at the human CCR4 receptor stably expressed in Chinese hamster ovary (CHO) cells was investigated. MDC alone was unable to elicit a Ca2+(i) response, but pre-stimulation of cells with ATP enabled a subsequent MDC-mediated Ca2+(i) response with a pEC50 of 8.66+/-0.16. The maximal response elicited by MDC was dependent upon the concentration of ATP used to prime, but the pEC50 was stable at all ATP concentrations tested. Pertussis toxin pre-treatment did not effect the ATP response, but abolished that to MDC, demonstrating that priming with ATP did not alter G protein-coupling specificity of the CCR4 receptor. Ionomycin and thapsigargin both increased Ca2+(i) concentrations (pEC50s of 7.59+/-0.57 and 6.81+/-0.31 respectively), but were unable to prime for MDC responses, suggesting the priming mechanism was not dependent upon increases in Ca2+(i) concentrations. Priming of the MDC response was still observed when experiments were performed with low Ca2+(e) (70 microM), indicating that Ca2+ influx was not required for ATP to prime the CCR4 receptor. Neither Ro31-8220 nor wortmannin affected priming, suggesting that protein kinase C and phosphoinositol 3-kinase were not involved. In conclusion, pre-stimulation of endogenous P2Y receptors with ATP facilitates Ca2+ signalling at the recombinant CCR4 receptor in CHO cells, although the mechanism by which this occurs remains to be defined.

Adenosine Triphosphate↗
PubMed2004

Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells.

Chemokines and their receptors play a pivotal role in controlling T cell trafficking in immunity and inflammation. Two chemokines, CCL17 and CCL22, activate the chemokine receptor CCR4, expressed on functionally distinct subsets of T cells: cutaneous leukocyte-associated antigen (CLA)+ skin-homing, T helper (Th) 2, and CD25+ T suppressor cells. Here, we compared the ability of CCL17 and CCL22 to promote CCR4 internalization as a mechanism of regulation of receptor function on human Th2 cells. We report that CCL22 is a potent and rapid inducer of CCR4 internalization, while CCL17 is not. CCR4 internalization does not require G protein coupling, while being dependent on lipid rafts integrity and clathrin-coated pits functionality. Cell surface disappearance of CCR4 is rapidly reversed upon removal of exogenous ligand by virtue of receptor recycling. CCR4 internalization leads to a loss of functional responsiveness, while recovery of surface expression leads to re-acquisition of chemotactic sensitivity of Th2 cells. The differential CCR4 desensitization and internalization reported here and the distinct expression patterns of CCL17 and CCL22 observed in vivo suggest that while CCL17 may act first on CCR4 at the endothelial surface to promote vascular recognition, CCL22 could subsequently engage the receptor within the tissue microenvironment to guide cellular localization.

Chemokine CCL17↗
PubMed2005

Identification of chemokine receptor CCR4 antagonist.

The present study reports the identification and hits to leads optimization of chemokine receptor CCR4 antagonists. Compound 12 is a high affinity, non-cytotoxic antagonist of CCR4 that blocks the functional activity mediated by the receptor.

Receptors, CCR4↗
PubMed2001

Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells.

Chemokines dictate regional trafficking of functionally distinct T cell subsets. In rodents and humans, a unique subset of CD4(+)CD25(+) cytotoxic T lymphocyte antigen (CTLA)-4(+) regulatory T cells (Treg) has been proposed to control peripheral tolerance. However, the molecular basis of immune suppression and the trafficking properties of Treg cells are still unknown. Here, we determined the chemotactic response profile and chemokine receptor expression of human blood-borne CD4(+)CD25(+) Treg cells. These Treg cells were found to vigorously respond to several inflammatory and lymphoid chemokines. Treg cells specifically express the chemokine receptors CCR4 and CCR8 and represent a major subset of circulating CD4(+) T cells responding to the chemokines macrophage-derived chemokine (MDC)/CCL22, thymus and activation-regulated chemokine (TARC)/CCL17, I-309/CCL1, and to the virokine vMIP-I (ligands of CCR4 and CCR8). Blood-borne CD4(+) T cells that migrate in response to CCL1 and CCL22 exhibit a reduced alloproliferative response, dependent on the increased frequency of Treg cells in the migrated population. Importantly, mature dendritic cells preferentially attract Treg cells among circulating CD4(+) T cells, by secretion of CCR4 ligands CCL17 and CCL22. Overall, these results suggest that CCR4 and/or CCR8 may guide Treg cells to sites of antigen presentation in secondary lymphoid tissues and inflamed areas to attenuate T cell activation.

Abatacept↗
PubMed1999

The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells.

Lymphocytes that are responsible for regional (tissue-specific) immunity home from the blood to the intestines, inflamed skin or other sites through a multistep process involving recognition of vascular endothelial cells and extravasation. Chemoattractant cytokine molecules known as chemokines regulate this lymphocyte traffic, in part by triggering arrest (stopping) of lymphocytes rolling on endothelium. Here we show that many systemic memory T cells in blood carry the chemokine receptor CCR4 and therefore respond to its ligands, the chemokines TARC and MDC. These cells include essentially all skin-homing cells expressing the cutaneous lymphocyte antigen and a subset of other systemic memory lymphocytes; however, intestinal (alpha4beta7+) memory and naive T cells respond poorly. Immunohistochemistry reveals anti-TARC reactivity of venules and infiltration of many CCR4+ lymphocytes in chronically inflamed skin, but not in the gastrointestinal lamina propria. Moreover, TARC induces integrin-dependent adhesion of skin (but not intestinal) memory T cells to the cell-adhesion molecule ICAM-1, and causes their rapid arrest under physiological flow. Our results suggest that CCR4 and TARC are important in the recognition of skin vasculature by circulating T cells and in directing lymphocytes that are involved in systemic as opposed to intestinal immunity to their target tissues.

Chemokine CCL17↗
PubMed2006

RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4.

Chemokines are now known to play an important role in cancer growth and metastasis. Here we report that differentiating osteoclasts constitutively produce CCL22 (also called macrophage-derived chemokine) and potentially promote bone metastasis of lung cancer expressing its receptor CCR4. We first examined expression of chemokines by differentiating osteoclasts. CCL22 was selectively upregulated in osteoclast-like cells derived from RAW264.7 cells and mouse bone marrow cells upon stimulation with RANKL (receptor activator of nuclear factor-kappaB ligand). In addition, a human lung cancer cell line SBC-5 that efficiently metastasized to bone when intravenously injected into NK cell-depleted SCID mice was found to express CCR4. Stimulation of SBC-5 cells with CCL22 induced cell migration and also enhanced phosphorylation of protein kinase B/Akt and extracellular signal-regulated kinase (ERK). Furthermore, immunohistochemical analysis of bone metastasis lesions demonstrated close co-localization of tartrate-resistant alkaline phosphatase (TRAP)-positive osteoclasts expressing CCL22 and SBC-5 cells expressing CCR4. Collectively, these results suggest that osteoclasts may promote bone metastasis of cancer cells expressing CCR4 in the bone marrow by producing its ligand CCL22.

Animals↗
PubMed2003

Expression of the T-helper 2-specific chemokine receptor CCR4 on CCR10-positive lymphocytes in atopic dermatitis skin but not in psoriasis skin.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases. AD is generally perceived as a T-helper (Th) 2-dominated disease whereas psoriasis is a Th1-dominated disease. The chemokine cutaneous T-cell attracting chemokine (CTACK) and its receptor CCR10 attract skin-homing lymphocytes to inflamed skin, suggesting that CCR10+ cells in AD and psoriasis should be of Th2 and Th1 type, respectively. The chemokine receptor CCR4 is expressed selectively on Th2 lymphocytes and its ligand thymus and activation-regulated chemokine (TARC) is upregulated in AD lesions, suggesting that the CCR10+ cells in AD lesions should also express CCR4. OBJECTIVES: To examine the coexpression of CCR10 and CCR4 on skin-invading lymphocytes in AD and psoriasis lesions as well as the Th1/Th2 cytokine expression of the CCR10+ lymphocytes. METHODS: Skin biopsies from AD and psoriasis patients were double stained with antibodies against CCR10-CCR4, CCR10-CCR5, CCR10-interleukin (IL)-2 and CCR10-IL-4. RESULTS: The CCR10+ cells in AD showed a mixed IL-2/IL-4 expression pattern, and a minor proportion expressed CCR4, whereas a large proportion of the CCR4+ cells did not express CCR10. In psoriasis the CCR10+ cells only expressed IL-2, and no CCR4 expression was detected. CONCLUSIONS: The CCR10+ lymphocytes invading the skin in AD and psoriasis have different Th1/Th2 profiles, as measured by both their cytokine and chemokine receptor expression. This suggests that the CCR10+ subpopulation of lymphocytes is made up of different Th1/Th2 subsets. However, the Th1/Th2 lymphocytes of AD and psoriasis were either CCR10+ or CCR10-, suggesting that both the Th1 and Th2 subpopulation can be subdivided further. CCR4 was found only in AD skin and on both CCR10+ and CCR10- cells, supporting the hypothesis of TARC and CTACK as being independent lymphocyte-attracting chemokines in AD.

Adult↗
PubMed2005

Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7.

BACKGROUND: Adhesion molecules and chemokine receptors are involved in tissue-specific homing of T cells to the skin and play an important role in the pathophysiology of cutaneous lymphoma. It has recently been reported that the chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the chemokine receptor CCR10. OBJECTIVES: To investigate the expression of CCR4, CCR7 and CCR10 on skin-homing CLA(+) and CD4(+) T cells in the peripheral blood of patients with Sezary syndrome (SS), a rare leukaemic variant of cutaneous T-cell lymphoma. METHODS: Lymphocytes from five patients with SS, six patients with mycosis fungoides and four healthy volunteers were isolated and analysed using flow cytometry. Additionally, the T-cell receptor (TCR)-Vbeta CDR3 regions were cloned and sequenced in two patients. RESULTS: We found that CCR4 is expressed on almost all CLA(+) and CD4(+) memory T cells. Using monoclonal antibodies specific for single TCR-Vbeta chains we identified malignant T cells in four patients with SS. Importantly, we found that most but not all malignant Sezary cells expressed the skin-homing chemokine receptor CCR10. Additionally, we found that a significant proportion of these cells also expressed the lymph node-homing chemokine receptor CCR7. CONCLUSIONS: Our results support the concept that chemokine receptors play an important role in the pathophysiology of SS and suggest that the malignant clone may represent an expansion of skin-homing cutaneous 'central' memory T cells in the peripheral blood of these patients.

Adult↗
PubMed2006

Core exploration in optimization of chemokine receptor CCR4 antagonists.

The design, synthesis, and SAR studies of 'core' variations led to identification of novel, selective, and potent small molecule antagonist (22) of the CC chemokine receptor-4 (CCR4) with improved in vitro activity and liability profile. Compound 22 was efficacious in a murine allergic inflammation model (ED50 approximately 10 mg/kg).

Animals↗
PubMed2002

Differential expression of thymus and activation regulated chemokine and its receptor CCR4 in nodal and cutaneous anaplastic large-cell lymphomas and Hodgkin's disease.

Recent studies demonstrated that Hodgkin/Reed-Sternberg (H/RS) cells in Hodgkin's disease (HD) express thymus and activation-regulated chemokine (TARC), whereas reactive lymphocytes surrounding H/RS cells express its ligand, CC-chemokine receptor 4 (CCR4). Because in vitro studies showed that CCR4 expression is a marker for lymphocytes bearing a T-helper 2 (Th2) phenotype, it was suggested that expression of TARC is a new immune escape mechanism in HD. To find out whether this mechanism might also be operative in CD30+ malignant lymphomas other than HD, TARC and CCR4 expression was investigated by immunohistochemistry on paraffin and frozen-tissue sections of 39 nodal CD30+ anaplastic large cell lymphomas (ALCL), including 27 ALK-negative and 12 ALK-positive ALCL, 25 primary cutaneous CD30+ ALCL, including 11 patients with lymphomatoid papulosis, and 31 cases of HD. TARC was expressed by the neoplastic cells in 12/27 (44%) nodal ALK-negative ALCL and all cases of classic HD, but not in nodal ALK-positive ALCL (0/12) and only rarely in primary cutaneous CD30+ ALCL (3/25). In contrast, CCR4 was expressed by the neoplastic cells in 9/9 cutaneous CD30+ ALCL, and in 9/15 (60%) nodal ALK-negative ALCL, but only in 1/4 (25%) nodal ALK-positive ALCL and not by the H/RS cells in HD (0/8). Apart from three cases of HD showing 10 to 15% CCR4-positive lymphocytes surrounding TARC-positive H/RS cells, CCR4-positive reactive T cells were few (<5%) in all other cases studied. Our results demonstrate a differential expression of TARC and CCR4 in different types of CD30+ malignant lymphomas. The small number of CCR4-positive reactive T cells in most cases studied argues against an important role of TARC expression in the evasion of antitumor responses.

Alkaline Phosphatase↗
PubMed2005

Role of the chemokine receptor CCR4 and its ligand thymus- and activation-regulated chemokine/CCL17 for lymphocyte recruitment in cutaneous lupus erythematosus.

Skin-infiltrating T lymphocytes are thought to play a major role in the pathogenesis of cutaneous lupus erythematosus (CLE). In this study, we investigated the role of the chemokine receptor 4 (CCR4) and its ligand thymus- and activation-regulated chemokine (TARC/CCL17) for the recruitment of T cells in inflamed skin of patients with CLE. We found significant numbers of CCR4+ T lymphocytes in the skin of all patients with CLE. Interestingly, a subset of patients with disseminated scarring skin involvement were characterized by both lesional and circulating CD8+ T cells expressing CCR4. Destruction of epidermal and adnexal structures was histomorphologically associated with CCR4+ cytotoxic T cells invading basal layers of the epidermis where keratinocytes showed apoptotic death. The CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and elevated in the serum of CLE patients. The functional relevance of lymphocytic CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration assays. Our investigations suggest that CCR4 and TARC/CCL17 play a role in the pathophysiology of CLE. In particular, cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE.

Adult↗
PubMed2001

The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics.

In vitro polarized human Th2 cells preferentially express the chemokine receptors CCR3, CCR4, and CCR8 and migrate to their ligands: eotaxin, monocyte-derived chemokine (MDC), thymus- and activation-regulated chemokine (TARC), and I-309. We have studied the expression of chemokines and chemokine receptors in the airway mucosa of atopic asthmatics. Immunofluorescent analysis of endobronchial biopsies from six asthmatics, taken 24 hours after allergen challenge, demonstrates that virtually all T cells express IL-4 and CCR4. CCR8 is coexpressed with CCR4 on 28% of the T cells, while CCR3 is expressed on eosinophils but not on T cells. Expression of the CCR4-specific ligands MDC and TARC is strongly upregulated on airway epithelial cells upon allergen challenge, suggesting an involvement of this receptor/ligand axis in the regulation of lymphocyte recruitment into the asthmatic bronchi. In contrast to asthma, T cells infiltrating the airways of patients with chronic obstructive pulmonary disease and pulmonary sarcoidosis produce IFN-gamma and express high levels of CXCR3, while lacking CCR4 and CCR8 expression. These data support the role of CCR4, of its ligands MDC and TARC, and of CCR8 in the pathogenesis of allergen-induced late asthmatic responses and suggest that these molecules could be considered as targets for therapeutic intervention.

Asthma↗
PubMed2001

Chemokine receptor CCR4 on CD4+ T cells in juvenile rheumatoid arthritis synovial fluid defines a subset of cells with increased IL-4:IFN-gamma mRNA ratios.

To understand the mechanisms that promote recruitment and survival of T cells within the pediatric inflamed joint, we have studied the expression of CCR4 and CCR5 on synovial fluid T cells and matched peripheral blood samples from juvenile rheumatoid arthritis (JRA) patients using three-color flow cytometric analysis. Thymus- and activation-regulated chemokine and macrophage-derived chemokine, ligands for CCR4, were measured by ELISA in JRA synovial fluid, JRA plasma, adult rheumatoid arthritis synovial fluid, and normal plasma. IL-4 and IFN-gamma mRNA production was assessed in CD4+/CCR4+ and CD4+/CCR4(-) cell subsets. We found accumulations of both CCR4+ and CCR5+ T cells in JRA synovial fluids and a correlation for increased numbers of CCR4+ T cells in samples collected early in the disease process. Thymus- and activation-regulated chemokine was detected in JRA synovial fluid and plasma samples, but not in adult rheumatoid arthritis synovial fluid or control plasma. Macrophage-derived chemokine was present in all samples. CD4+/CCR4+ synovial lymphocytes produced more IL-4 and less IFN-gamma than CD4+/CCR4(-) cells. These findings suggest that CCR4+ T cells in the JRA joint may function early in disease in an anti-inflammatory capacity through the production of type 2 cytokines and may play a role in determining disease phenotype.

Adolescent↗
PubMed1998

Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells.

Polarized Th1 and Th2 cells differentially express adhesion molecules and chemokine receptors, endowing these cells with distinct tissue homing capabilities. Here we report that, in contrast to other chemokine receptors, the expression of CCR4 and CCR8 on Th2 cells is transiently increased following TCR and CD28 engagement. IL-4 is not required for this activation-induced up-regulation of CCR4 and CCR8. In accordance with receptor expression, the response of Th2 cells to I-309 (CCR8 ligand) and thymus- and activation-regulated chemokine (CCR4 and CCR8 ligand) is enhanced upon activation. Moreover, activated Th1 cells up-regulate CCR4 expression and functional responsiveness to thymus- and activation-regulated chemokine. Analysis of polarized subsets of CD8+ T cells reveals a similar pattern of chemokine receptor expression and modulation of responsiveness. Taken together, these findings suggest that an up-regulation of CCR4 and CCR8 following Ag encounter may contribute to the proper positioning of activated T cells within sites of antigenic challenge and/or specialized areas of lymphoid tissues.

Calcium↗
PubMed2002

Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes.

Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4(+) lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4(+) populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue-infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4(+) lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra-lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69(+)). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in alpha(4)beta(7) expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1999

High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma.

Hodgkin's lymphoma is characterized by the combination of Reed-Sternberg (R-S) cells and a prominent inflammatory cell infiltrate. One of the intriguing questions regarding this disease is what is causing the influx of T lymphocytes into the involved tissues. We applied the serial analysis of gene expression (SAGE) technique on the Hodgkin's lymphoma-derived cell line L428 and on an Epstein-Barr virus (EBV)-transformed lymphoblastoid B-cell line. A frequently expressed tag in L428 corresponded to the T-cell-directed CC chemokine TARC. Reverse transcription polymerase chain reaction analyses demonstrated expression of TARC in nodular sclerosis (NS) and mixed cellularity (MC) classical Hodgkin's lymphomas but not in NLP Hodgkin's lymphoma, anaplastic large-cell lymphomas, and large-B-cell lymphomas with CD30 positivity. Two of five cases of T-cell-rich B-cell lymphoma (TCRBCL) were TARC positive. RNA in situ hybridization (ISH) showed a strong signal for TARC in the cytoplasm of R-S cells, and immunohistochemical staining confirmed the presence of the TARC protein in the R-S cells of NS and MC Hodgkin's lymphomas. The lymphocytic and histiocytic (L&H)-type cells of nodular lymphocyte predominance Hodgkin's lymphoma and the neoplastic cells of non-Hodgkin's lymphomas with the exception of two cases of TCRBCL did not stain for TARC. TARC is known to bind to the CCR4 receptor, which is expressed on activated Th2 lymphocytes. The immunophenotype of lymphocytes surrounding R-S cells is indeed Th2-like, and by RNA ISH these lymphocytes showed a positive signal for the chemokine receptor CCR4. The findings suggest that production of TARC by the R-S cells may explain the characteristic T-cell infiltrate in classical Hodgkin's lymphoma.

B-Lymphocytes↗
PubMed2000

Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets.

Platelets are known to contain platelet factor 4 and beta-thromboglobulin, alpha-chemokines containing the CXC motif, but recent studies extended the range to the beta-family characterized by the CC motif, including RANTES and Gro-alpha. There is also evidence for expression of chemokine receptors CCR4 and CXCR4 in platelets. This study shows that platelets have functional CCR1, CCR3, CCR4, and CXCR4 chemokine receptors. Polymerase chain reaction detected chemokine receptor messenger RNA in platelet RNA. CCR1, CCR3, and especially CCR4 gave strong signals; CXCR1 and CXCR4 were weakly positive. Flow cytometry with specific antibodies showed the presence of a clear signal for CXCR4 and weak signals for CCR1 and CCR3, whereas CXCR1, CXCR2, CXCR3, and CCR5 were all negative. Immunoprecipitation and Western blotting with polyclonal antibodies to cytoplasmic peptides clearly showed the presence of CCR1 and CCR4 in platelets in amounts comparable to monocytes and CCR4 transfected cells, respectively. Chemokines specific for these receptors, including monocyte chemotactic protein 1, macrophage inflammatory peptide 1alpha, eotaxin, RANTES, TARC, macrophage-derived chemokine, and stromal cell-derived factor 1, activate platelets to give Ca(++) signals, aggregation, and release of granule contents. Platelet aggregation was dependent on release of adenosine diphosphate (ADP) and its interaction with platelet ADP receptors. Part, but not all, of the Ca(++) signal was due to ADP release feeding back to its receptors. Platelet activation also involved heparan or chondroitin sulfate associated with the platelet surface and was inhibited by cleavage of these glycosaminoglycans or by heparin or low molecular weight heparin. These platelet receptors may be involved in inflammatory or allergic responses or in platelet activation in human immunodeficiency virus infection.

Adenosine Diphosphate↗
PubMed2006

Antagonists of CCR4 as immunomodulatory agents.

The chemokine receptor CCR4 is broadly expressed on cells of the immune system. It is known to play a central role in T cell migration to the thymus, and T cell maturation and education. In addition, CCR4 is known to modulate T cell migration to several sites of inflammation in the body, including the skin, and lungs. It is best known as a drug target for airway inflammation and atopic dermatitis, but cells expressing CCR4 are found in many inflammatory diseases. CCR4 small molecule antagonists have not yet reached the clinic, but at least one has been validated in an in vivo model. Here we review the current status of structurally novel CCR4 receptor antagonists.

Animals↗