Dataset Information

B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury.

ABSTRACT: Acute kidney injury (AKI) is a serious condition affecting one fifth of hospital inpatients. B lymphocytes have immunological functions beyond Ab production and may produce cytokines and chemokines that modulate inflammation. In this study, we investigated leukocyte responses in a mouse model of AKI and observed an increase in circulating and kidney B cells, particularly a B220low subset, following AKI. We found that B cells produce the chemokine CCL7, with the potential to facilitate neutrophil and monocyte recruitment to the injured kidney. Siglec-G-deficient mice, which have increased numbers of B220low innate B cells and a lower B cell activation threshold, had increased Ccl7 transcripts, increased neutrophil and monocyte numbers in the kidney, and more severe AKI. CCL7 blockade in mice reduced myeloid cell infiltration into the kidney and ameliorated AKI. In two independent cohorts of human patients with AKI, we observed significantly higher CCL7 transcripts compared with controls, and in a third cohort, we observed an increase in urinary CCL7 levels in AKI, supporting the clinical importance of this pathway. Together, our data suggest that B cells contribute to early sterile inflammation in AKI via the production of leukocyte-recruiting chemokines.

SUBMITTER: Inaba A

PROVIDER: S-EPMC7444279 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury.

Inaba Akimichi A Tuong Zewen K ZK Riding Alexandra M AM Mathews Rebeccah J RJ Martin Jack L JL Saeb-Parsy Kourosh K Clatworthy Menna R MR

Journal of immunology (Baltimore, Md. : 1950) 20200731 5

Acute kidney injury (AKI) is a serious condition affecting one fifth of hospital inpatients. B lymphocytes have immunological functions beyond Ab production and may produce cytokines and chemokines that modulate inflammation. In this study, we investigated leukocyte responses in a mouse model of AKI and observed an increase in circulating and kidney B cells, particularly a B220<sup>low</sup> subset, following AKI. We found that B cells produce the chemokine CCL7, with the potential to facilitate ...[more]

PMID: 32737150

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Project description:BackgroundRatios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease.MethodsIn this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment.ResultsAt baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 × 106 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005).ConclusionsIn contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity.Trial registrationClinicaltrials.gov NCT02712424 . Date of registration: March 14, 2016.

Project description:BackgroundThe preoperative peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have been reported to be associated with the prognosis of various cancers but are always discussed separately. The aim of this study is to bring the combination of NLR, PLR and MLR into the prognostic assessment system of endometrial cancer (EC) and establish a nomogram to provide an objective prediction model for clinical decisions.MethodsA total of 1111 patients with EC who had accepted surgical treatment during 2013-2017 were involved in the analysis. Their NLR, PLR, and MLR levels were obtained from a routine blood examination within 2 weeks before operation. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs. Chi-square tests analysed the associations of the ratios with other clinicopathological variables. The prognostic value was indicated by overall survival (OS) via Cox proportional hazards models and Kaplan-Meier analysis. R software was used to establish the nomogram based on the combination of NLR, PLR, MLR and other clinicopathological factors.ResultsThe median follow-up period was 40 months, and the median age was 56. The enrolled patients were stratified by cutoffs of 2.14 for NLR, 131.82 for PLR and 0.22 for MLR. Multivariate analyses demonstrated that high NLR over 2.14 (HR = 2.71, 95%CI = 1.83-4.02, P<0.001), high PLR over 131.82 (HR = 2.75, 95%CI = 1.90-3.97, P<0.001), and high MLR over 0.22 (HR = 1.72, 95%CI = 1.20-2.45, P = 0.003) were significantly associated with worse OS. The combined indicator, high NLR + high PLR + high MLR (HR = 4.34, 95%CI = 2.54-7.42, P<0.001), showed the highest prognostic value. The Harrell's concordance index of the nomogram was 0.847 (95% CI = 0.804-0.890), showing good discrimination and calibration of this model.ConclusionThe combination of NLR, PLR, and MLR is a superior prognostic factor of EC. The nomogram involving the combination of NLR, PLR, MLR and other clinicopathological factors is recommended to predict OS for EC patients clinically.

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Dataset Information

B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury.

Publications

B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury.

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