Chemokines: attractive mediators of the immune response

Wong, Mark; Fish, Eleanor N.

doi:10.1016/s1044-5323(02)00123-9

Cited by 226 publications

(188 citation statements)

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“…26 (ii) RANTES is one of the activation factors of Erk and p38 members of the mitogen-activated protein kinase (MAPK) family that are involved in regulating cell proliferation and differentiation. 17,25,27,28 Interestingly, p38 is considered to be a master switch between benign and destructive insulitis and therefore provokes the development of T1D. 29 Inhibition of p38 MAPK leads to the inhibition of Th1 immunity and prevents NOD mice from developing diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…13,14 In addition to the trafficking effect, RANTES, like other CC chemokines, plays an important role in co-stimulation of T-cell proliferation 15,16 and activation of the T cells localized in the inflammatory lesion. 17 Activation of T cells by RANTES leads to interleukin-2 (IL-2) receptor expression, cytokine release and T-cell proliferation. 16 Micromolar concentrations of RANTES can induce T-cell proliferation in an antigenindependent manner that is especially important in autoimmunity, whereas the increased level of RANTES in the inflammatory sites may lead to the enhanced activation and proliferation of local T cells.…”

Section: Introductionmentioning

confidence: 99%

“…16 Micromolar concentrations of RANTES can induce T-cell proliferation in an antigenindependent manner that is especially important in autoimmunity, whereas the increased level of RANTES in the inflammatory sites may lead to the enhanced activation and proliferation of local T cells. 17 Recent studies suggest that RANTES is also involved in the process of Tcell differentiation. Administration of RANTES and its interaction with the CCR5 receptor bias the T-helper response toward a T-helper type 1 (Th1)-associated cytokine profile.…”

Section: Introductionmentioning

confidence: 99%

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Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

et al. 2006

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RANTES (regulated on activation, normal T-cell expressed and secreted) is a T-helper type 1 (Th1) chemokine that promotes T-cell activation and proliferation. RANTES is genetically associated with asthma, sarcoidosis and multiple sclerosis. The concentration of RANTES is increased at inflammation sites in different autoimmune diseases. Type 1 diabetes (T1D) is a Th1-mediated disease with complex genetic predisposition. We tested RANTES as a candidate gene for association with T1D using three single-nucleotide polymorphism (SNP) variants (rs4251719, rs2306630 and rs2107538) to capture haplotype information. The minor alleles of all SNPs were transmitted less frequently to T1D offspring (transmission rates 37.3% (P ¼ 0.002), 38.7% (P ¼ 0.007) and 41.0% (P ¼ 0.01)) and were less frequently present in patients compared to controls (P ¼ 0.009, 0.03 and 0.04, respectively). A similar protective effect was observed for the haplotype carrying three minor alleles (transmission disequilibrium test (TDT): P ¼ 0.003; odds ratio (OR) ¼ 0.55; confidence interval (CI): 0.37-0.83; case/control: P ¼ 0.03; OR ¼ 0.74; CI: 0.55-0.98). Both patients and controls carrying the protective haplotype express significantly lower serum levels of RANTES compared to non-carriers. Subsequently, we tested a cohort of 310 celiac disease patients, but failed to detect association. RANTES SNPs are significantly associated with RANTES serum concentration and development of T1D. The rs4251719*A-rs2306630*A-rs2107538*A haplotype associated with low RANTES production confers protection from T1D. Our data imply that RANTES is associated with T1D both genetically and functionally, and contributes to diabetesprone Th1 cytokine profile.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

et al. 2006

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“…In the present study, 67 pathways that were statistically significant were identified, and several of them have been proven by other researchers. For example, 'Chemokine signaling pathway (path:ssc04062)' (Table 2) was discovered to be a mediator of immunity (Le et al, 2004) and has also been proven to be related to cell growth and differentiation (Wong and Fish, 2003). A similar situation has also been found in the most significant pathway -'Cytokine-cytokine receptor interaction (path:ssc04060)' (Deverman and Patterson, 2009).…”

Section: Pleiotropy Of Growth and Immunity On Meishan Pigsmentioning

confidence: 93%

“…The reason is that some immune processes or cytokines play roles in cancer regulation, and the growth of functional biological molecules can also play an important part in tumor growth, such as with 'Proteoglycans in cancer (path:ssc05205).' Furthermore, the significant pathway 'Jak-STAT signaling pathway (path: ssc04630)' plays an important role in growth and immunity because many cytokines and growth factors mediate their effects via activation of this pathway (Wong and Fish, 2003).…”

Section: Pleiotropy Of Growth and Immunity On Meishan Pigsmentioning

confidence: 99%

Identification of pleiotropic genes and gene sets underlying growth and immunity traits: a case study on Meishan pigs

Zhang

Wang

Yang

et al. 2016

animal

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Both growth and immune capacity are important traits in animal breeding. The animal quantitative trait loci (QTL) database is a valuable resource and can be used for interpreting the genetic mechanisms that underlie growth and immune traits. However, QTL intervals often involve too many candidate genes to find the true causal genes. Therefore, the aim of this study was to provide an effective annotation pipeline that can make full use of the information of Gene Ontology terms annotation, linkage gene blocks and pathways to further identify pleiotropic genes and gene sets in the overlapping intervals of growth-related and immunity-related QTLs. In total, 55 non-redundant QTL overlapping intervals were identified, 1893 growth-related genes and 713 immunity-related genes were further classified into overlapping intervals and 405 pleiotropic genes shared by the two gene sets were determined. In addition, 19 pleiotropic gene linkage blocks and 67 pathways related to immunity and growth traits were discovered. A total of 343 growth-related genes and 144 immunity-related genes involved in pleiotropic pathways were also identified, respectively. We also sequenced and genotyped 284 individuals from Chinese Meishan pigs and European pigs and mapped the single nucleotide polymorphisms (SNPs) to the pleiotropic genes and gene sets that we identified. A total of 971 high-confidence SNPs were mapped to the pleiotropic genes and gene sets that we identified, and among them 743 SNPs were statistically significant in allele frequency between Meishan and European pigs. This study explores the relationship between growth and immunity traits from the view of QTL overlapping intervals and can be generalized to explore the relationships between other traits.

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Biology of CCR5 and Its Role in HIV Infection and Treatment

Lederman¹,

Penn-Nicholson²,

Cho³

et al. 2006

JAMA

227

164

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Chemokine receptors are found on cell surfaces and promote cellular migration by chemotaxis. The CC chemokine receptor 5 (CCR5) is used by the human immunodeficiency virus (HIV) to infect cells. Strategies that target human CCR5 are therefore being developed to prevent and treat HIV infection. Antiviral strategies that target a host element necessary for viral replication may be predicted to interfere with the function of that element and may therefore adversely affect the host. We conducted a review of the literature between November 2005 and April 2006 with a focus on articles addressing the genetics and function of CCR5, the effects of CCR5 deletion in human and murine systems, and treatment strategies for HIV infection that target this coreceptor. English-language articles in the human and murine literature published between March 1996 and April 2006 were identified through a search of MEDLINE using CCR5 as the search term. Relevant articles as judged by their titles and abstracts were reviewed in detail. In addition, based on our knowledge of the field and with permission, unpublished work was also reviewed. In this article, we explore the effects that targeting CCR5 may have on host defenses in individuals with immunity already compromised by HIV infection.

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Chemokines: attractive mediators of the immune response

Cited by 226 publications

References 109 publications

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

Identification of pleiotropic genes and gene sets underlying growth and immunity traits: a case study on Meishan pigs

Biology of CCR5 and Its Role in HIV Infection and Treatment

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