IL-18 Acts in Synergy with IL-7 To Promote Ex Vivo Expansion of T Lymphoid Progenitor Cells

Gandhapudi, Siva K.; Tan, Chibing; Marino, Julie H.; Taylor, Ashlee; Pack, Christopher C.; Gaikwad, Joel; Wiele, C. Justin Van De; Wren, Jonathan D.; Teague, T. Kent

doi:10.4049/jimmunol.1301542

Cited by 17 publications

(13 citation statements)

References 54 publications

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“…The expression of IL-18Rα by ILCPs may be functionally important, as it enables them to sense IL-18 induced by tissue inflammation. It has also been reported that hematopoietic stem cells, common lymphoid progenitors, and early thymic progenitors express IL-18Rα (Gandhapudi et al, 2015). IL-18 plus IL-7 promotes the expansion of hematopoietic stem cells and common lymphoid progenitors, and IL-18 alone can promote differentiation of early thymic progenitors into double-negative stage 3 in vitro.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets

Ghaedi

Shen

Orangi

et al. 2019

Journal of Experimental Medicine

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Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. ILC2 development is dependent on the transcription factor retinoic acid receptor–related orphan receptor (RORα), which is also expressed in common ILC progenitors. To elucidate the developmental pathways of lung ILC2s, we generated RORα lineage tracer mice and performed single-cell RNA sequencing, flow cytometry, and functional analyses. In adult mouse lungs, we found an IL-18Rα+ST2− population different from conventional IL-18Rα−ST2+ ILC2s. The former was GATA-3intTcf7EGFP+Kit+, produced few cytokines, and differentiated into multiple ILC lineages in vivo and in vitro. In neonatal mouse lungs, three ILC populations were identified, namely an ILC progenitor population similar to that in adult lungs and two distinct effector ILC2 subsets that differentially produced type 2 cytokines and amphiregulin. Lung ILC progenitors might actively contribute to ILC-poiesis in neonatal and inflamed adult lungs. In addition, neonatal lung ILC2s include distinct proinflammatory and tissue-repairing subsets.

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Section: Discussionmentioning

confidence: 99%

Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets

Ghaedi

Shen

Orangi

et al. 2019

Journal of Experimental Medicine

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“…GAMMA’s performance has been previously benchmarked by predicting Gene Ontology annotations for 5,000 genes and then comparing the predictions to their known Gene Ontology annotations [ 12 , 16 ]. Importantly, predicted phenotypes and functions from GAMMA have also been validated experimentally in several published studies [ 16 – 21 ].…”

Section: Methodsmentioning

confidence: 99%

Genetic Variation in the Platelet Endothelial Aggregation Receptor 1 Gene Results in Endothelial Dysfunction

et al. 2015

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Platelet Endothelial Aggregation Receptor 1 (PEAR1) is a newly identified membrane protein reported to be involved in multiple vascular and thrombotic processes. While most studies to date have focused on the effects of this receptor in platelets, PEAR1 is located in multiple tissues including the endothelium, where it is most highly expressed. Our first objective was to evaluate the role of PEAR1 in endothelial function by examining flow-mediated dilation of the brachial artery in 641 participants from the Heredity and Phenotype Intervention Heart Study. Our second objective was to further define the impact of PEAR1 on cardiovascular disease computationally through meta-analysis of 75,000 microarrays, yielding insights regarding PEAR1 function, and predictions of phenotypes and diseases affected by PEAR1 dysregulation. Based on the results of this meta-analysis we examined whether genetic variation in PEAR1 influences endothelial function using an ex vivo assay of endothelial cell migration. We observed a significant association between rs12041331 and flow-mediated dilation in participants of the Heredity and Phenotype Intervention Heart Study (P = 0.02). Meta-analysis results revealed that PEAR1 expression is highly correlated with several genes (e.g. ANG2, ACVRL1, ENG) and phenotypes (e.g. endothelial cell migration, angiogenesis) that are integral to endothelial function. Functional validation of these results revealed that PEAR1 rs12041331 is significantly associated with endothelial migration (P = 0.04). Our results suggest for the first time that genetic variation of PEAR1 is a significant determinant of endothelial function through pathways implicated in cardiovascular disease.

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“…Protein C was selected from a list of potential biomarkers output by the GAMMA analysis as predicted to be associated with VTE risk. To date, GAMMA has been used successfully to validate phenotypes and disease relevance for several previously uncharacterized or poorly characterized genes [15–19]. While protein C is known to decrease after chemotherapy [20], there is paucity of prospective data measuring the value of this biomarker as a predictor of cancer-associated thrombosis.…”

Section: Introductionmentioning

confidence: 99%

Prospective evaluation of protein C and factor VIII in prediction of cancer-associated thrombosis

Tafur

Dale

Cherry

et al. 2015

Thrombosis Research

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Venous thromboembolism (VTE) is a preventable disease, yet it is one of the leading causes of death among patients with cancer. Improving risk stratification mechanisms will allow us to personalize thromboprophylaxis strategies. We sought to evaluate Collagen and Thrombin Activated Platelets (COAT-platelets) as well as protein C and factor VIII as biomarkers predictive of cancer-associated thrombosis in a prospective cohort of patients with cancer. Protein C was selected as a candidate based on bioinformatics prediction. Blood samples were collected before chemotherapy. All specimen processing was blinded to clinical data. Surveillance and adjudication of the main outcome of VTE was performed for up to 1 year. We used Cox proportional hazard regression to measure the association of biomarkers and incident events using SAS 9.2 for all statistical analysis. Death was modeled as a competing event. Among 241 patients followed for an average of 10.4 months, 15% died and 13% developed a VTE. COAT-platelets were not predictive of VTE. Low levels of pre-chemotherapy protein C (< 118 %) (HR 2.5; 95%CI 1.1–5.5) and high baseline factor VIII (> 261 % I) (HR 3.0; 95%CI 1.1–8.0) were predictive of VTE after adjusting for age, Khorana prediction risk, metastatic disease and D dimer. In addition, low protein C was predictive of overall mortality independent of age, metastatic disease and functional status (HR 2.8; 95%CI 1.3–6.0). Addition of these biomarkers to Cancer-VTE risk prediction models may add to risk stratification and patient selection to optimize thrombo-prophylaxis.

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IL-18 Acts in Synergy with IL-7 To Promote Ex Vivo Expansion of T Lymphoid Progenitor Cells

Cited by 17 publications

References 54 publications

Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets

Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets

Genetic Variation in the Platelet Endothelial Aggregation Receptor 1 Gene Results in Endothelial Dysfunction

Prospective evaluation of protein C and factor VIII in prediction of cancer-associated thrombosis

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