Disease relevance of CCL17

• Selective induction of Th2-attracting chemokines CCL17 and CCL22 in human B cells by latent membrane protein 1 of Epstein-Barr virus [1].
• Role of the chemokine receptor CCR4 and its ligand thymus- and activation-regulated chemokine/CCL17 for lymphocyte recruitment in cutaneous lupus erythematosus [2].
• On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients [3].
• CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis [3].
• TSLP and TARC/CCL17 expression correlated with airway obstruction [4].

High impact information on CCL17

• 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 [5].
• 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 [5].
• Importantly, mature dendritic cells preferentially attract Treg cells among circulating CD4(+) T cells, by secretion of CCR4 ligands CCL17 and CCL22 [6].
• To establish the pathophysiological roles of TARC in vivo, we investigated whether a monoclonal antibody (mAb) against TARC could inhibit the induction of hepatic lesions in murine model using Propionibacterium acnes and lipopolysaccharide (LPS) [7].
• Pivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice [7].

Chemical compound and disease context of CCL17

• Immunolocalization of bleomycin-treated lung tissue and human idiopathic pulmonary fibrosis tissue specimens showed that epithelial cells expressed CCL17 [8].
• Plasma TARC levels were significantly increased in patients with AD (P <.0001) and showed significant correlations with severity scoring of atopic dermatitis (SCORAD) index (r = 0.665, P <.00001), serum lactate dehydrogenese levels (r = 0.696, P =.00001), eosinophil counts (r = 0.381, P =.007), and platelet counts (r = 0.562, P <.0001) [9].
• However, as the role of IL-8 in oral cancer cells is unclear, this study is thus designed to examine IL-8 secretion in cultured oral epidermoid carcinoma KB CCL17 cells treated with nicotine and/or arecoline [10].
• Dimensions of the luminal thrombus and the arc of aneurysm wall covered by thrombus (TARC) [11].

Biological context of CCL17

• CCL17 and CCL22 had the highest signals in RS cells at gene expression and at protein levels [12].
• To explore this relationship in greater detail, we have more precisely localized the MDC gene to chromosome 16q13, the same position reported for the TARC gene [13].
• In addition, the genes for MDC and TARC are encoded by human chromosome 16 [13].
• BAL fluids were analyzed for total cell counts and differentials, and supernatants were assayed by ELISA for levels of TARC, MDC, and I-309 [14].
• Consistent with this, ovalbumin (OVA) specific IgE levels, which reflect the T-B cell interaction, are significantly correlated with the amounts of TARC and MDC in sera [15].

Anatomical context of CCL17

• Indeed, the secreted CCL17 and CCL22, both associated with the migration of Treg cells to peripheral tissues, were also detected in the biopsies [16].
• The selective production of CCL17 and CCL22 by M-DCs but not P-DCs was confirmed in vivo by immunohistology on human reactive lymph node sections [17].
• TARC/CCL17 is produced by the keratinocytes in AD lesions, and CCR4 is overexpressed on CLA+ (cutaneous lymphocyte-associated antigen) lymphocytes in the skin and blood [18].
• CXCL12 can be secreted by endothelial cells and is present in atherosclerotic plaques, whereas CCL17 and CCL22 are secreted by monocytes and macrophages [19].
• Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages [3].

Associations of CCL17 with chemical compounds

• Although both CCL17 and CCL22 caused mobilization of intracellular calcium, none of them induced migration or histamine release [20].
• Roxithromycin (RXM), a 14-membered ring macrolide, suppressed CCL17 production by HaCaT KC induced by IFNgamma and TNFalpha [21].
• Surprisingly, an inhibitor of epidermal growth factor receptor tyrosine kinase, PD153035, enhanced the production of CCL17 in HaCaT KC [21].
• Inhibitors for nuclear factor kappa B (NFkappaB), parthenolide, and Bay 11-7085, and an inhibitor of p38, SB202190, inhibited TNFalpha- and IFNgamma-induced production of CCL17 by HaCaT KC [21].
• However, after E(2) pretreatment the lipopolysaccharide (LPS)-induced production of MCP-1, TARC, and MDC by DCs was clearly enhanced [22].

Physical interactions of CCL17

• TARC also bound to the promiscuous chemokine receptor on erythrocytes (Kd, 17 nM) [23].
• TARC is known to bind to the CCR4 receptor, which is expressed on activated Th2 lymphocytes [24].
• Collectively, T cells express a highly selective receptor for TARC that is coupled to pertussis toxin-sensitive G-protein [23].

Regulatory relationships of CCL17

• OBJECTIVE: We sought to determine whether transforming growth factor-beta 1 (TGF-beta 1) regulated TARC expression in keratinocytes [25].
• IFN-gamma further enhanced the IL-4+TNF-alpha or IL-13+TNF-alpha-induced TARC production in the fibroblasts [26].
• Clonal Th2 cells associated with chronic hypereosinophilia: TARC-induced CCR4 down-regulation in vivo [27].
• To determine whether polymorphisms of the IL-4Ralpha have an impact on the ability of IL-13 or IL-4 to induce TARC release, HASM cells from multiple donors were genotyped for the Ile50Val, Ser478Pro, and Gln551Arg polymorphisms of the IL-4Ralpha [28].
• T-cell-directed chemokine thymus- and activation-regulated chemokine (TARC)- and/or macrophage-derived chemokine (MDC)-positive H&RS cells were detected in all 20 cases of HL MC and HL NS but only in 5 of 9 cases of HL-like ATLL [29].

Other interactions of CCL17

• Viral macrophage inflammatory protein (vMIP)-I, I-309, and TARC competed with the binding of (125)I-309 to AD cells with varying affinities [30].
• K562 cells stably expressing CCR4 also responded to TARC in a calcium mobilization assay [31].
• Thymus and activation-regulated chemokine (TARC) is a recently identified CC chemokine that is expressed constitutively in thymus and transiently in stimulated peripheral blood mononuclear cells [31].
• Systemic CXCL9 levels decreased from pre- to grass pollen season in allergics (P < 0.05), whereas CCL17 decreased in non-allergics (P < 0.05) over the same period [32].
• There was no correlation between plasma levels of MCP-1/CCL2 and TARC/CCL17 [33].

Analytical, diagnostic and therapeutic context of CCL17

• Furthermore, serum CCL17 and CXCL10 levels varied between AML patients and were determined by disease status (both chemokines) as well as patient age, chemotherapy and complicating infections (only CCL17) [34].
• METHODS: We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks [35].
• Furthermore, we detected strong signals for CCR4, TARC, and MDC in ATL skin lesions by RT-PCR [36].
• We could not find any significant relationship of IP-10, Mig, I-TAC and TARC gene expression with disease-free survival or lower risk of recurrence after surgery [37].
• Peak expression of CCL22 preceded the peak levels of CCL17, as measured by real-time quantitative PCR [8].

References