Cloning and Characterization of a Novel Murine Macrophage Inflammatory Protein-1α Receptor

Meyer, Angela; Coyle, Anthony J.; Proudfoot, Amanda E. I.; Wells, Timothy N.C.; Power, Christine

doi:10.1074/jbc.271.24.14445

Cited by 27 publications

(24 citation statements)

References 32 publications

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“…CCR5 has multiple ligands, among them CCL4 (12), which is involved in the modulation of the recruitment/retention of T R cells to activated antigen-presenting cells (11). We build on this finding by demonstrating that in transwell migration assays CCL4 predominantly acts on CCR5 ϩ effector T R cells rather than on the T R cell population as a whole.…”

Section: Discussionmentioning

confidence: 95%

“…CCR5 appears to be the only cognate receptor for CCL4 (12). Given the previously shown role of CCL4 in the trafficking of T R cells (11), we examined their expression of CCR5.…”

Section: Ccr5mentioning

confidence: 99%

“…Although it remains unclear which chemokine receptor is responsible for the CCL4-mediated effects on T R cells, biochemical studies have shown CCL4 to bind to the chemokine receptor CCR5 (12). Expression of CCR5 on T cells has been associated with both proinflammatory and antiinflammatory T cell function in mouse and human.…”

mentioning

confidence: 99%

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Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus

Kallikourdis

Andersen

Welch

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

129

114

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Regulatory T cells play an essential role in preventing fetal rejection by the maternal immune system. Here we show that, based on the expression of CCR5, regulatory T cells can be divided into a highly suppressive CCR5 ؉ and a far less suppressive CCR5 ؊ subpopulation, suggesting that the former represent the effector arm of regulatory T cells. Although regulatory T cells from CCR5 ؊/؊ gene deletion mutants still suppress, they are less effective mediators of maternal-fetal tolerance. The accumulation of CCR5 ؉ regulatory T cells at this site appears to be enhanced by alloantigen. This finding is in stark contrast to the systemic expansion of regulatory T cells during pregnancy, which appears to be alloantigenindependent. The fact that CCR5 ؉ regulatory T cells preferentially accumulate in the gravid uterus and that expression of CCR5 on regulatory T cells can be induced by activation lead us to propose that CCR5 is responsible for the accumulation of those regulatory T cells that have been activated by paternal antigens.effector T cells ͉ pregnancy ͉ tolerance ͉ chemokine receptor R egulatory T cells (T R cells) play an important role in the maintenance of peripheral tolerance and the prevention of autoimmunity (1). Where T R cells exert their suppressive function and what attracts them to and retains them at their site of action is poorly understood. Inducible T R cells (Tr1-like cells) have a preference for skin homing (2), whereas naturally occurring Foxp3 ϩ T R cells can be found in all lymphoid organs (3, 4). The CD103 ϩ subpopulation of T R cells has been shown to home to the site of inflammation (5); however, the mechanism by which this occurs remains elusive.Previously, we have demonstrated that naturally occurring T R cells mediate maternal tolerance to the fetus and can be found in the uterus during pregnancy (6). Although the uterine accumulation of macrophages (7), natural killer cells (8, 9), and eosinophils (10) has been extensively studied, there has been no insight on how T R cells find their way to the gravid uterus.Upon activation, professional antigen-presenting cells express the chemokine CCL4, which leads to the recruitment and/or retention of T R cells (11). Although it remains unclear which chemokine receptor is responsible for the CCL4-mediated effects on T R cells, biochemical studies have shown CCL4 to bind to the chemokine receptor CCR5 (12). Expression of CCR5 on T cells has been associated with both proinflammatory and antiinflammatory T cell function in mouse and human. CCR5 is thought to be expressed on antigen-experienced, effector T cells that home toward sites of inflammation outside the secondary lymphoid organs (13-15). CCR5 ϩ T cells have been shown to infiltrate inflamed sites such as the synovium of rheumatoid arthritis patients (16,17) and the central nervous system of mice with experimental autoimmune encephalomyelitis (18). Expression of CCR5 in pancreatic islets correlates with increased severity of diabetes in mice (19), and CCR5 is thought to mediate T cell migratio...

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Section: Discussionmentioning

confidence: 95%

“…CCR5 appears to be the only cognate receptor for CCL4 (12). Given the previously shown role of CCL4 in the trafficking of T R cells (11), we examined their expression of CCR5.…”

Section: Ccr5mentioning

confidence: 99%

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Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus

Kallikourdis

Andersen

Welch

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

129

114

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“…RN31 is CCR-1, FG15 is CCR-2 (homologous to human CCR-2b form), G17 is CCR-3, D2 is CCR-4, RN3 is CCR-5, and ME is the CCR-1-like orphan receptor MIP-1␣RL1 (Refs. [53][54][55][56][57]. In addition, we have also identified a novel receptor, D6, which shows homology to these and other members of the subfamily of G-protein-coupled chemokine receptors.…”

Section: Identification Of Murine Chemokine Receptors From Genomicmentioning

confidence: 93%

Cloning and Characterization of a Novel Murine β Chemokine Receptor, D6

Nibbs

Wylie

Pragnell

et al. 1997

Journal of Biological Chemistry

128

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“…The CCR5 receptor for RANTES (28) is preferentially expressed by Th1 lymphocytes (29)(30)(31). Additional ligands for CCR5 are MIP-1α and MIP-1β, both of which were upregulated in the pancreata of RIP-IL12 tg mice.…”

Section: Discussionmentioning

confidence: 99%

Constitutive β cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes

Holz¹,

Brett²,

Oldstone³

2001

J. Clin. Invest.

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Cloning and Characterization of a Novel Murine Macrophage Inflammatory Protein-1α Receptor

Cited by 27 publications

References 32 publications

Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus

Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus

Cloning and Characterization of a Novel Murine β Chemokine Receptor, D6

Constitutive β cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes

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Cloning and Characterization of a Novel Murine Macrophage Inflammatory Protein-1α Receptor

Cited by 27 publications

References 32 publications

Alloantigen-enhanced accumulation of CCR5+‘effector’ regulatory T cells in the gravid uterus

Alloantigen-enhanced accumulation of CCR5+‘effector’ regulatory T cells in the gravid uterus

Cloning and Characterization of a Novel Murine β Chemokine Receptor, D6

Constitutive β cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes

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Product

Resources

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Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus

Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus