Genomic Organization of the CC Chemokine MIP-3α/CCL20/LARC/EXODUS/SCYA20, Showing Gene Structure, Splice Variants, and Chromosome Localization

Nelson, Robin T.; Boyd, James G.; Gladue, Ronald P.; Paradis, Timothy; Thomas, Ranjeny; Cunningham, Ann; Lira, Paul D.; Brissette, William H.; Hayes, Lisa S.; Hames, Lynn M.; Neote, Kuldeep; McColl, Shaun R.

doi:10.1006/geno.2001.6482

Cited by 44 publications

(42 citation statements)

References 41 publications

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“…Unlike other CC chemokines, SCYA20 was localized to chromosome 2q33–q372 using a combination of PCR analysis of single chromosome DNA hybrids, yeast artificial chromosome clones, and radiation hybrid mapping (4, 14). The full length of human CCL20 cDNA contains 799 bp (4 exons and 3 introns), encoding an open reading frame of 95 or 96 AA (14–16). Since the putative cleavage site of this precursor protein is between Ala-26 and Ala-27, the mature form is a polypeptide with a length of 70 AA (14).…”

Section: The Ccl20-ccr6 Axismentioning

confidence: 99%

CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology and Inflammatory Bowel Disease: Odd Couple or Axis of Evil?

Lee¹,

Eri²,

Lyons³

et al. 2013

Front. Immunol.

107

108

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Chemokines and their cognate receptors have been identified as major factors initiating and governing cell movement and interaction. These ligands and their receptors are expressed on a wide variety of cells and act during steady-state migration as well as inflammatory recruitment. CCR6 is a non-promiscuous chemokine receptor that has only one known chemokine ligand, CCL20, and is present on B and T cells as well as dendritic cells (DCs). Two CD4+ T cell populations with opposing functions present in the intestines and the mesenteric lymph nodes express CCR6: the pro-inflammatory TH17 and regulatory Treg cells. CCL20 is also present in the intestine and is strongly up-regulated after an inflammatory stimulus. Interestingly, this ligand is also expressed by TH17 cells, which opens up the possibility of autocrine/paracrine signaling and, consequently, a self-perpetuating cycle of recruitment, thereby promoting inflammation. Recently, CCR6 has been implicated in inflammatory bowel disease (IBD) by genome wide association studies which showed an association between SNPs in the genomic region of the CCR6 gene and the inflammation. Furthermore, recent research targeting the biological function of CCR6 indicates a significant role for this chemokine receptor in the development of chronic IBD. It is therefore possible that IBD is facilitated by a disordered regulation of TH17 and Treg cells due to a disruption in the CCL20-CCR6 axis and consequently disturbed mucosal homeostasis. This review will summarize the literature on CCL20-CCR6 in mucosal immunology and will analyze the role this receptor-ligand axis has in chronic IBD.

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Section: The Ccl20-ccr6 Axismentioning

confidence: 99%

CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology and Inflammatory Bowel Disease: Odd Couple or Axis of Evil?

Lee¹,

Eri²,

Lyons³

et al. 2013

Front. Immunol.

107

108

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“…28 A partial rat CXCR3 cDNA was amplified by degenerate RT-PCR using primers based on published human and mouse CXCR3 Genbank entries (NP_001495 and O88410, respectively). Sequencing of the amplified PCR product revealed that it was highly homologous to both mouse and human CXCR3.…”

Section: Cloning Of Rat Cxcl11 and Cxcr3mentioning

confidence: 99%

“…Rat CXCL11 was chemically synthesized as previously described 28 and tested for activity in vitro. The synthetic protein was found to mobilize intracellular calcium in human CXCR3-expressing cell lines with similar potency to human CXCL11, and to heterologously cross-desensitize the receptor to human CXCL10 (data not shown).…”

Section: Biological Activity Of Cxcl11 In Vitromentioning

confidence: 99%

Expression of rat I-TAC/CXCL11/SCYA11 during central nervous system inflammation: comparison with other CXCR3 ligands

McColl

Mahalingam

Staykova

et al. 2004

Laboratory Investigation

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The chemokines are a large gene superfamily with critical roles in development and immunity. The chemokine receptor CXCR3 appears to play a major role in the trafficking of activated Th1 lymphocytes. There are at least three major ligands for CXCR3: mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, and of these three ligands, CXCL11 is the least well-characterized. In this study, we have cloned a rat ortholog of CXCL11, evaluated its function, and examined its expression in the Th-1-mediated disease, experimental autoimmune encephalomyelitis (EAE) in the rat. Based on its predicted primary amino-acid sequence, rat I-TAC/CXCL11 was synthesized and shown to induce chemotaxis of activated rat T lymphocytes in vitro and the in vivo migration of T lymphocytes when injected into the skin. I-TAC/CXCL11 expression, as determined by RT-PCR, increased in lymph node and spinal cord tissue collected from rats in which EAE had been actively induced, and in spinal cord tissue from rats in which EAE had been passively induced. The kinetics of expression were similar to that of CXCR3 and IP-10/CXCL10, although expression of both CXCR3 and IP-10/CXCL10 was more intense than that of I-TAC/CXCL11 and increased more rapidly in both lymph nodes and the spinal cord. Only minor levels of expression of the related chemokine mig/CXCL9 were observed. Immunohistochemistry revealed that the major cellular source of I-TAC/CXCL11 in the central nervous system (CNS) during EAE is likely to be the astrocyte. Together, these data indicate that I-TAC/CXCL11 is expressed in the CNS during the clinical phase of EAE. However, the observation that I-TAC/CXCL11 is expressed after receptor expression is detected suggests that it is not essential for the initial migration of CXCR3-bearing cells into the CNS.

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“…Upregulation of EGFRs has been observed in corneal epithelial cells exposed to similar EFs, an effect possibly mediated by TNF- α [54]. TNF- α may also be responsible for increased expression of CCL20, which functions to recruit inflammatory cells to tissue and has been found to be expressed in epidermal cells with disrupted barrier function and therefore in the presence of EFs [13, 27, 41]. Increased expression of cytokines and chemokines may also result in the upregulation of leukemia inhibitory factor (LIF), which then may reinforce upregulation of cytokines, particularly interleukins [14, 48].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of chemokine (C–C motif) ligand 20 in adult epidermal keratinocytes in direct current electric fields

2009

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Electric fields (EFs) of around 100 mV/mm are present in normal healing wounds and induce the directional migration of epithelial cells. Reepithelialization during wound healing thus may be controlled in part by this electrical signal. In this study, the early transcriptional response of human epidermal keratinocytes to EFs is examined using microarrays. Increased expression of various chemokines, interleukins, and other inflammatory response genes indicates that EFs stimulate keratinocyte activation and immune stimulatory activity. Gene expression activity further suggests that interleukin 1 is either released or activated in EFs. Expression of the chemokine CCL20 steadily increases at 100 mV/mm over time until around 8 h after exposure. This chemokine is also expressed at field strengths of 300 mV/mm—above the level of endogenous wound fields. The early effects of EFs on epithelial gene expression activity identified in these studies suggest the importance of naturally occurring EFs both in repair mechanisms and for the possibility of controlling these responses therapeutically.

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Genomic Organization of the CC Chemokine MIP-3α/CCL20/LARC/EXODUS/SCYA20, Showing Gene Structure, Splice Variants, and Chromosome Localization

Cited by 44 publications

References 41 publications

CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology and Inflammatory Bowel Disease: Odd Couple or Axis of Evil?

CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology and Inflammatory Bowel Disease: Odd Couple or Axis of Evil?

Expression of rat I-TAC/CXCL11/SCYA11 during central nervous system inflammation: comparison with other CXCR3 ligands

Upregulation of chemokine (C–C motif) ligand 20 in adult epidermal keratinocytes in direct current electric fields

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