Peripheral Tissue Chemokines: Homeostatic Control of Immune Surveillance T Cells

McCully, Michelle L.; Kouzeli, Ariadni; Moser, Bernhard

doi:10.1016/j.it.2018.06.003

Cited by 28 publications

(39 citation statements)

References 148 publications

(83 reference statements)

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“…In fact, we know that CXCL14 is down-regulated under inflammatory conditions ( 2 , 7 ), ruling out a primary influence on the recruitment of short-lived effector leukocytes. Of interest, CXCL14 and CXCL12 are the most highly conserved members of the large family of chemokines and mice lacking these chemokines have severe developmental defects [reviewed in McCully et al and Nagasawa ( 1 , 60 )]. It is possible that CXCL14 and CXCL12 synergize during organ development, including neurovascular patterning ( 61 ), eye ( 62 ) and connective tissue ( 63 ) formation, where both chemokines are prominently expressed.…”

Section: Discussionmentioning

confidence: 99%

“…CXCL14 is one of the least understood chemokines, featuring remarkable amino acid sequence conservation across a wide range of species and constitutive expression in border-lining tissues by epithelial cells, fibroblasts and macrophages ( 1 ). The study of target cells for CXCL14, and hence its role in physiological and pathophysiological processes, has been hampered by the lack of identification of its receptor.…”

Section: Introductionmentioning

confidence: 99%

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CXCL14 Preferentially Synergizes With Homeostatic Chemokine Receptor Systems

et al. 2020

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Reflecting their importance in immunity, the activity of chemokines is regulated on several levels, including tissue and context-specific expression and availability of their cognate receptor on target cells. Chemokine synergism, affecting both chemokine and chemokine receptor function, has emerged as an additional control mechanism. We previously demonstrated that CXCL14 is a positive allosteric modulator of CXCR4 in its ability to synergize with CXCL12 in diverse cellular responses. Here, we have extended our study to additional homeostatic, as well as a selection of inflammatory chemokine systems. We report that CXCL14 strongly synergizes with low (sub-active) concentrations of CXCL13 and CCL19/CCL21 in in vitro chemotaxis with immune cells expressing the corresponding receptors CXCR5 and CCR7, respectively. CXCL14 by itself was inactive, not only on cells expressing CXCR5 or CCR7 but also on cells expressing any other known conventional or atypical chemokine receptor, as assessed by chemotaxis and/or β-arrestin recruitment assays. Furthermore, synergistic migration responses between CXCL14 and inflammatory chemokines CXCL10/CXCL11 and CCL5, targeting CXCR3 and CCR5, respectively, were marginal and occasional synergistic Ca 2+ flux responses were observed. CXCL14 bound to 300-19 cells and interfered with CCL19 binding to CCR7-expressing cells, suggesting that these cellular interactions contributed to the reported CXCL14-mediated synergistic activities. We propose a model whereby tissue-expressed CXCL14 contributes to cell localization under steady-state conditions at sites with prominent expression of homeostatic chemokines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CXCL14 Preferentially Synergizes With Homeostatic Chemokine Receptor Systems

et al. 2020

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“…GDM is also identified as a pre-diabetic clinical condition offering a unique opportunity to study abnormalities that may occur during initial stages of the fetal development [36,37]. Four main subfamilies of chemokines nominated as CC, CXC, CX3C and C are identified, to date [38][39][40]. It is now well evidenced that members of cytokine/chemokine network are critically involved in patho-physiology of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Serum concentration of angiogenic (CXCL1, CXCL12) and angiostasis (CXCL9, CXCL10) CXC chemokines are differentially altered in normal and gestational diabetes mellitus associated pregnancies

Darakhshan

Fatehi

Hassanshahi

et al. 2019

J Diabetes Metab Disord

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Background The present study was aimed and designed to determine the serum levels of CXCL1 and CXCL12 as angiogenesis along with CXCL9 and CXCL10 as angiostasis, chemokines in, Gestational diabetes mellitus mothers (GDMM) and normal pregnancy mothers (NPM) and neonates who delivered by them. Methods We have recruited 63 pregnant GDMM and 63 normal pregnant mothers at the third trimester of pregnancy to this cross-sectional study. Cord blood specimens were obtained from neonates who were delivered from GDMM and NPM. The serum and cord blood levels of chemokines were measured by ELISA in studied groups. Data were analyzed by chi-square and student's t test between two groups. The P-values less than 0.05 were considered significant. Results Our results revealed that the serum levels of CXCL1, CXCL9 and CXCL12 were increased in GDMM, while no alteration was found in the serum levels of CXCL10 when compared to NPM. We have observed that in neonates the serum levels of angiogeneic chemokines followed an inverse fashion when compared to angiostasis chemokines. Interestingly, CXCL1 and CXCL12 were both increased in neonates who were delivered by GDMM, while, CXCL9 and CXCL10 were decreased in neonates delivered by GDMM. Keywords CXCL1. CXCL9. CXCL10. CXCL12. Chemokine. Gestational diabetes mellitus Abbreviations APGAR is a quick test performed on delivered infants at 1 and 5 min after birth BMI Body mass index FBS Fasting blood sugar GCT Glucose challenge test GDM Gestational diabetes mellitus INF Interferon PAI-1, Plasminogen activator inhibitor-1 TNF-α Tumor necrosis factor-α T2DM Type 2 diabetes mellitus MetS Metabolic syndrome HbA1C The hemoglobin A1C ELISA Enzyme linked immunosorbent assay SPSS Statistical package for the Social sciences GDMM Gestational diabetes mellitus mothers NPM Normal pregnancy mothers * Mojgan Noroozi Karimabad

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“…Looking at the general protein categories, an increase of angiogenic regulators is expected to broadly contribute to improved vascularization [73,74] and through this increased perfusion of tissues, to tissue repair. Immune regulators promote better surveillance and wound clearance in multiple tissues [75,76]. Increases in neurotrophic growth factors BDNF and CNTF, and of GDF5 which broadly and positively regulates formation of cartilage, brown fat, and neuronal axons and dendrites, have implications for better maintenance and repair of damage in the CNS and periphery.…”

Section: Introductionmentioning

confidence: 99%

Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin

Mehdipour

Skinner

Wong

et al. 2020

Aging

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Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a "neutral" age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.

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Peripheral Tissue Chemokines: Homeostatic Control of Immune Surveillance T Cells

Cited by 28 publications

References 148 publications

CXCL14 Preferentially Synergizes With Homeostatic Chemokine Receptor Systems

CXCL14 Preferentially Synergizes With Homeostatic Chemokine Receptor Systems

Serum concentration of angiogenic (CXCL1, CXCL12) and angiostasis (CXCL9, CXCL10) CXC chemokines are differentially altered in normal and gestational diabetes mellitus associated pregnancies

Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin

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