scholarly journals Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease

2021 ◽  
Author(s):  
Sibylle von Vietinghoff ◽  
Christian Kurts
Keyword(s):  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Transplant Rejection ◽  
Human Kidney ◽  
Experimental Models ◽  
Cellular Interactions ◽  
Inflammatory Conditions ◽  
Renal Candidiasis ◽  
And Function ◽  
Receptor Cx3cr1

AbstractAttraction, retention, and differentiation of leukocytes to and within the kidney are governed by chemokines. The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1 are exemplary in this regard as they are highly expressed and further upregulated in a range of kidney diseases. CX3CL1 is chiefly produced by renal endothelium and tubular epithelium, where it promotes leukocyte attraction. Recent data suggest that in addition to established soluble mediators, cellular interactions may enhance CX3CL1 expression. The receptor CX3CR1 is essential in myeloid phagocyte homing to the kidney at homeostasis, after acute cell depletion and in inflammation. CX3CR1 and its ligand are highly regulated in human kidney diseases such as IgA nephritis, systemic lupus erythematosus, and inflammatory conditions such as transplant rejection. A mechanistic role of CX3CR1 has been established in experimental models of nephrotoxic nephritis and renal candidiasis. It is debated in fibrosis. Recent publications demonstrate a role for CX3CR1+ myeloid cells in radio-contrast-agent and sepsis-induced kidney damage. Systemically, circulating CX3CR1+ monocytes reversibly increase in individuals with renal impairment and correlate with their cardiovascular risk. In this review, we discuss role and regulatory mechanisms of the CX3CL1-CX3CR1 axis in both localized and systemic effects of renal inflammation.

scholarly journals Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney Diseases

2020 ◽  
Vol 31 (6) ◽  
pp. 1178-1190 ◽  
Author(s):  
Daniyal J. Jafree ◽  
David A. Long
Keyword(s):  
Kidney Disease ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Transplant Rejection ◽  
Lymphatic Vessels ◽  
Renal Physiology ◽  
Clear Fluid ◽  
Adult Kidney ◽  
And Function ◽  
Development Structure

The kidney contains a network of lymphatic vessels that clear fluid, small molecules, and cells from the renal interstitium. Through modulating immune responses and via crosstalk with surrounding renal cells, lymphatic vessels have been implicated in the progression and maintenance of kidney disease. In this Review, we provide an overview of the development, structure, and function of lymphatic vessels in the healthy adult kidney. We then highlight the contributions of lymphatic vessels to multiple forms of renal pathology, emphasizing CKD, transplant rejection, and polycystic kidney disease and discuss strategies to target renal lymphatics using genetic and pharmacologic approaches. Overall, we argue the case for lymphatics playing a fundamental role in renal physiology and pathology and treatments modulating these vessels having therapeutic potential across the spectrum of kidney disease.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Anna Julie Peired ◽  
Alessandro Sisti ◽  
Paola Romagnani
Keyword(s):  
Clinical Trials ◽  
Kidney Disease ◽  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Human Kidney ◽  
Consensus Protocol ◽  
Paracrine Factors ◽  
Cell Based Therapy

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose.

scholarly journals Tissue-specific control of galectin-1-driven circuits during inflammatory responses

Glycobiology ◽  
2021 ◽  
Author(s):  
Anabela M Cutine ◽  
Camila A Bach ◽  
Florencia Veigas ◽  
Joaquín P Merlo ◽  
Lorena Laporte ◽  
...  
Keyword(s):  
Potential Role ◽  
Inflammatory Responses ◽  
Binding Protein ◽  
Experimental Models ◽  
Tissue Specific ◽  
Inflammatory Conditions ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Specific Control

Abstract The relevance of glycan-binding protein in immune tolerance and inflammation has been well established, mainly by studies of C-type lectins, siglecs and galectins both in experimental models and patient samples. Galectins, a family of evolutionarily conserved lectins, are characterized by sequence homology in the carbohydrate-recognition domain (CRD), atypical secretion via an ER-Golgi-independent pathway and the ability to recognize β-galactoside-containing saccharides. Galectin-1 (Gal-1), a prototype member of this family displays mainly anti-inflammatory and immunosuppressive activities, although, similar to many cytokines and growth factors, it may also trigger paradoxical pro-inflammatory effects under certain circumstances. These dual effects could be associated to tissue-, time- or context-dependent regulation of galectin expression and function, including particular pathophysiologic settings and/or environmental conditions influencing the structure of this lectin, as well as the availability of glycosylated ligands in immune cells during the course of inflammatory responses. Here, we discuss the tissue-specific role of Gal-1 as a master regulator of inflammatory responses across different pathophysiologic settings, highlighting its potential role as a therapeutic target. Further studies designed at analyzing the intrinsic and extrinsic pathways that control Gal-1 expression and function in different tissue microenvironments may contribute to design tailored therapeutic strategies aimed at positively or negatively modulate this glycan-binding protein in pathologic inflammatory conditions.

scholarly journals Expression of the fractalkine receptor (CX3CR1) in human kidney diseases

2002 ◽  
Vol 62 (2) ◽  
pp. 488-495 ◽  
Author(s):  
Stephan Segerer ◽  
Erik Hughes ◽  
Kelly L. Hudkins ◽  
Matthias Mack ◽  
Tracy Goodpaster ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Human Kidney ◽  
Fractalkine Receptor ◽  
Receptor Cx3cr1

scholarly journals Complete Complement Components C4A and C4B Deficiencies in Human Kidney Diseases and Systemic Lupus Erythematosus

2004 ◽  
Vol 173 (4) ◽  
pp. 2803-2814 ◽  
Author(s):  
Yan Yang ◽  
Karl Lhotta ◽  
Erwin K. Chung ◽  
Paula Eder ◽  
Friedrich Neumair ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Human Kidney ◽  
Systemic Lupus ◽  
Complement Components

B lymphocytes can regulate the maturation and function of human dendritic cells but are partially inefficient in systemic lupus erythematosus

2012 ◽  
Vol 71 (Suppl 1) ◽  
pp. A34.1-A34
Author(s):  
Ahsen Morva ◽  
Sébastien Lemoine ◽  
Achouak Achour ◽  
Alain Saraux ◽  
Jacques-Olivier Pers ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
B Lymphocytes ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
And Function ◽  
Human Dendritic Cells

Monitoring Of Human Kidney Transplants Using Quantification Of Autologous 111Indium -Oxine Platelet Label Deposition - Beneficial Effect Of PGI2-Treatment In Acute (AR) And Chronic Rejection (CR)

1981 ◽  
Author(s):  
H Sinzinger ◽  
Ch Leithner ◽  
M Schwarz
Keyword(s):  
Early Diagnosis ◽  
Acute Rejection ◽  
Serum Creatinine ◽  
Beneficial Effect ◽  
Transplant Rejection ◽  
Human Kidney ◽  
Controlled Study ◽  
Platelet Deposition ◽  
Transplant Function ◽  
Diagnosis Of Rejection

Eighty patients with AR and chronic transplant rejection as well as with a stable transplant function were monitored by a combination of quantification of 111In-oxine labeled platelet uptake in the transplanted kidney (under γ- camera) and platelet survival (PS). In acute phase after transplantation the patients were controlled twice or three times a day until 3-4 weeks (weekly platelet labeling) after the transplantation. The quantification of platelet deposition (index (i): transplant region:contralateral region/cts. per 5 minutes) is demonstrated to be a very useful parameter of early diagnosis of rejection crisis. In AR i reaches values up to 2,00, the PS between 24 and 72 hours. In constant transplant function i below 1,20 are found, indicating that also in patients without any clinical sign of rejection, a platelet deposition and a shortening of PS occurs. In 8 patients with CR (i: 1,201,35; PS: 60-96 hours) and one week continuous i.v. PG2-administration (5ng PG2/kg/min) leads to a decrease in platelet deposition (i: minus 0,10-0,15) and a prolongation of PS. In 4 of these patients also the serum creatinine was decreased between 0,5 and 1,1 mg%. Using thereafter a combination of antiplatelet drugs we try now to retain the platelet deposition at the lower level reached by means of the PGI2application. Similar beneficial data could be obtained by treating acute rejection with PGI2-infusion. The preliminary data of a controlled study and the platelet function behaviour during PGI2 are reported.

scholarly journals P051 Symptoms of COVID-19 and anxiety levels in adult patients receiving b-and ts-DMARDS using an online reporting system

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
May Nwe Lwin ◽  
Christopher Holroyd ◽  
Dinny Wallis ◽  
Saul Faust ◽  
Hans De Graaf ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Joint Pain ◽  
Connective Tissue Diseases ◽  
Anxiety Score ◽  
Online Portal ◽  
Inflammatory Conditions ◽  
Advanced Therapy ◽  
Number Of Patients ◽  
Patient Reported ◽  
Anxiety Levels

Abstract Background/Aims  The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for over 120,000 UK deaths. Those with chronic inflammatory conditions or receiving immunosuppressive medications are at higher risk of COVID-19 than the general population. As a result, rheumatology patients taking b- or ts-DMARDs were advised to shield. We planned to observe COVID-19 related symptoms and anxiety levels reported by rheumatology patients during the pandemic. Methods  From April 2020, 1,004 rheumatology patients from an advanced therapy database were invited to participate in the adult ImmunoCOVID study to collect daily symptoms (fever, cough, shortness of breath (SOB), sore throat, blocked nose, red-eye, headache, fatigue, joint pain, muscle pain, chills, nausea, diarrhoea and vomiting, loss of senses) and anxiety level using an online portal. Loss of senses were not recorded until week 7 as these were not officially recognized at the pandemic onset. Results  153 patients (rheumatoid arthritis, n = 75, psoriatic arthritis, n = 28, Axial spondyloarthropathy, n = 24, systemic lupus erythematosus, n = 2 and other connective tissue diseases, n = 24) consented and participated. By week 25, 142 patients remained. Among those, 36.57% (±6.09%) (average (±SD)) reported no symptoms over the 25 week period. The main symptoms reported were joint pain (mean=47.94%) followed by fatigue (27.17%). Few patients reported fever (0.94%), cough (8.34%), SOB (4.53%), or loss of senses (1.11%) with more symptoms reported during the first 8 weeks (April/May 2020) and another increase in September/October 2020. The anxiety score (pragmatic 10-point scale) mean (±SD) was 5.60 (±0.34) and remained elevated throughout the study though higher when lockdown began. Conclusion  During the first peak of SARS-CoV-2, the number of patients reporting COVID-19 symptoms appeared high and was associated with high levels of anxiety. As only a small number have been swab-tested, this may suggest that larger numbers of untested individuals have had COVID-19 with mild symptoms. Features of inflammatory rheumatic illnesses may mimic COVID-19 symptoms and create diagnostic difficulty (joint pain and fatigue) whilst anxiety may lead to over-reporting of symptoms in the absence of infection. The key symptoms of fever, cough and SOB were less common and may be most reliable. Disclosure  M. Lwin: None. C. Holroyd: None. D. Wallis: None. S. Faust: None. H. De Graaf: None. C.J. Edwards: Honoraria; Abbvie, Biogen, BMS, Celgene, Fresenius, GSK, Janssen, Lilly, Mundipharma, Pfizer, Roche, Sanofi, UCB. Member of speakers’ bureau; Abbvie, Biogen, BMS, Celgene, Janssen, Lilly, Sanofi, Pfizer, Roche. Grants/research support; Abbvie, Biogen, Pfizer. P051 Table 1:patient reported symptoms and anxiety score from immunoCOVID studyWeek & (number of participants)Fever (%)Cough (%)SOB (%)Joint pain (%)Fatigue (%)Loss of senses (%)No symptoms (%)Tested (n)Test positive (n)Anxiety score1 (26)3.857.6911.5446.1530.77NA30.77006.312 (42)2.3311.639.3052.3834.88NA28.57005.833 (69)1.4514.494.3552.1737.68NA23.19415.884 (92)1.0911.966.5254.3531.52NA27.17206.225 (110)0.0011.716.3145.9533.33NA30.00006.156 (108)0.0010.193.7050.0026.85NA34.26205.747 (119)0.8410.084.2049.5828.57NA34.45205.938 (120)0.007.505.0051.6734.170.8329.17305.629 (124)0.817.263.2352.4229.840.8136.29405.6410 (118)0.008.473.3948.3129.660.8534.75205.2811 (116)0.858.476.7849.1529.661.6933.62305.6512 (131)0.006.114.5856.4926.720.7635.11205.4513 (110)0.916.362.7350.0029.091.8242.73105.4414 (121)0.837.442.4847.1125.620.8339.67805.2815 (100)1.007.003.0046.0023.001.0041.00405.4816 (114)0.887.893.5139.4725.441.7542.98905.2717 (105)0.008.573.8144.7622.860.9543.81425.1018 (107)0.006.543.7443.9319.630.9343.93405.3019 (99)0.005.052.0240.4019.191.0145.45505.0820 (110)0.914.552.7350.9124.550.9139.09NA0Missing data21 (106)0.946.602.8350.0020.750.9439.62405.2822 (104)2.889.626.7349.0430.770.9635.58305.5023 (106)1.897.553.7742.4526.420.9436.79805.8924 (108)0.938.332.7844.4422.220.9341.67605.6125 (94)1.067.454.2641.4915.962.1344.68605.49Average0.948.344.5347.9427.171.1136.575.60SD0.972.312.254.395.350.426.090.34Weekly data are the average of daily reported symptoms and anxiety levels.

scholarly journals A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Soudeh Moghadasi ◽  
Marischa Elveny ◽  
Heshu Sulaiman Rahman ◽  
Wanich Suksatan ◽  
Abduladheem Turki Jalil ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Ethical Issues ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Experimental Models ◽  
Live Cells ◽  
Target Cells ◽  
Intercellular Interaction ◽  
Micro Rnas

AbstractRecently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

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