CXCL17 Is Dispensable during Hypervirulent <i>Mycobacterium tuberculosis</i> HN878 Infection in Mice

Choreño-Parra, José Alberto; Dunlap, Micah; Swanson, Rosemary; Jiménez-Álvarez, Luis Armando; Muñoz-Torrico, Marcela; Guzmán-Beltrán, Silvia; Zúñiga, Joaquı́n; Khader, Shabaana A.

doi:10.4049/immunohorizons.2100048

Cited by 5 publications

(3 citation statements)

References 20 publications

(47 reference statements)

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“…Given reports of bactericidal and fungicidal activity against a variety of pathogens ( 16 ), GAG-bound CXCL17 is likely to form a first line of defense against microbes. Consistent with such a function, CXCL17 expression by epithelial cells has been reported to be induced following challenge of mice with Mycobacteria, although CXCL17-deficient mice were found to be no more susceptible to infection than wild-type littermates ( 71 ). CXCL17-deficient mice have also been reported to be less resistant to infection in a mouse model of herpes simplex virus infection, although this was postulated to be a result of impaired trafficking of GPR35 + cytotoxic T cells ( 72 ).…”

Section: Discussionmentioning

confidence: 80%

CXCL17 binds efficaciously to glycosaminoglycans with the potential to modulate chemokine signaling

Giblin,

Ranawana,

Hassibi

et al. 2023

Front. Immunol.

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IntroductionCXCL17 is a mucosally secreted protein, and the most recently identified human chemokine, an assignment based on protein fold prediction and chemotactic activity for leukocytes. However, these credentials have been the subject of much recent discussion and no experimental evidence has been presented regarding the definitive structure of CXCL17. In this study, we evaluated the structural and chemoattractant credentials of CXCL17 to better characterize this molecule, and gain deeper insights into its functional role as a glycosaminoglycan (GAG) binding protein.MethodsIn the absence of structural information, in silico modeling techniques assessed the likelihood of CXCL17 adopting a chemokine fold. Recombinant CXCL17 was synthesized in mammalian and prokaryotic systems. Modified Boyden chamber and real-time chemotaxis assays assessed the ability of CXCL17 to promote chemotaxis of murine splenocytes, human neutrophils, and CXCR1 transfectants. The efficacy of CXCL17 binding to GAGs was quantified with solid-phase assays and bio-layer interferometry techniquesResultsAll modeling efforts failed to support classification of CXCL17 as a chemokine based on its predicted conformation. Recombinant CXCL17 was observed to dimerize as a function of concentration, a characteristic of several chemokines. Contrary to a previous report, CXCL17 was not chemotactic for murine splenocytes, although it was a low-potency chemoattractant for human neutrophils at micromolar concentrations, several orders of magnitude higher than those required for CXCL8. As anticipated owing to its highly basic nature, CXCL17 bound to GAGs robustly, with key C-terminal motifs implicated in this process. While inactive via CXCR1, CXCL17 was found to inhibit CXCR1-mediated chemotaxis of transfectants to CXCL8 in a dose-dependent manner.DiscussionIn summary, despite finding little evidence for chemokine-like structure and function, CXCL17 readily bound GAGs, and could modulate chemotactic responses to another chemokine in vitro. We postulate that such modulation is a consequence of superior GAG binding, and that C-terminal fragments of CXCL17 may serve as prototypic inhibitors of chemokine function.

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Section: Discussionmentioning

confidence: 80%

CXCL17 binds efficaciously to glycosaminoglycans with the potential to modulate chemokine signaling

Giblin,

Ranawana,

Hassibi

et al. 2023

Front. Immunol.

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“…Cytokines and chemokines, along with growth factors, play an important and variable role in the immune system (Cameron and Kelvin 2003; Gong et al 2019; Rojewska et al 2019, Choreño‐Parra et al 2021) (Fig. 2).…”

Section: Role Of Cxcl17 In the Immune System And Related Phenomenamentioning

confidence: 99%

The cryptic role of CXCL17/CXCR8 axis in the pathogenesis of cancers: a review of the latest evidence

Hashemi

Khorramdelazad

2022

J. Cell Commun. Signal.

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Chemokines are immune system mediators that mediate various activities and play a role in the pathogenesis of several cancers. Among these chemokines, C‐X‐C motif chemokine 17 (CXCL‐17) is a relatively novel molecule produced along the airway epithelium in physiological and pathological conditions, and evidence shows that it plays a homeostatic role in most cases. CXCL17 has a protective role in some cancers and a pathological role in others, such as liver and lung cancer. This chemokine, along with its possible receptor termed G protein‐coupled receptor 35 (GPR35) or CXCR8, are involved in recruiting myeloid cells, regulating angiogenesis, defending against pathogenic microorganisms, and numerous other mechanisms. Considering the few studies that have been performed on the dual role of CXCL17 in human malignancies, this review has investigated the possible pro‐tumor and anti‐tumor roles of this chemokine, as well as future treatment options in cancer therapy.

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“…As a result of Mtb infection in both epithelial and myeloid cells, CXCL17 expression increases in latent human TB. However, in pulmonary TB, CXCL17 may be dispensable (Choreño‐Parra, Dunlap, et al, 2021).…”

Section: Cxcl17 Functions In Nonmalignant Diseasesmentioning

confidence: 99%

A comprehensive review of chemokine CXC17 (VCC1) in cancer, infection, and inflammation

Shabgah

Jadidi‐Niaragh

Ebrahimzadeh

et al. 2022

Cell Biology International

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A crucial component of the immune system are chemokiness. Chemokine's dysregulation has been linked to a number of pathological diseases. Recently, CXCL17, a chemokine belonging to the CXC subfamily, was identified. With regard to a number of physiological conditions and disorders, CXCL17 either has homeostatic or pathogenic effects. Some research suggests that CXCL17 is an orphan ligand, despite the fact that G protein-coupled receptor (GPR) 35 has been suggested as a possible receptor for CXCL17. Since CXCL17 is primarily secreted by mucosal epithelia, such as those in the digestive and respiratory tracts, under physiological circumstances, this chemokine is referred to as a mucosal chemokine.Macrophages and monocytes are the cells that express GPR35 and hence react to CXCL17. In homeostatic conditions, this chemokine has anti-inflammatory, antibacterial, and chemotactic properties. CXCL17 promotes angiogenesis, metastasis, and cell proliferation in pathologic circumstances like malignancies. However, other studies suggest that CXCL17 may have anti-tumor properties. Additionally, studies have shown that CXCL17 may have a role in conditions such as idiopathic pulmonary fibrosis, multiple sclerosis, asthma, and systemic sclerosis. Additionally,

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CXCL17 Is Dispensable during Hypervirulent Mycobacterium tuberculosis HN878 Infection in Mice

Cited by 5 publications

References 20 publications

CXCL17 binds efficaciously to glycosaminoglycans with the potential to modulate chemokine signaling

CXCL17 binds efficaciously to glycosaminoglycans with the potential to modulate chemokine signaling

The cryptic role of CXCL17/CXCR8 axis in the pathogenesis of cancers: a review of the latest evidence

A comprehensive review of chemokine CXC17 (VCC1) in cancer, infection, and inflammation

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