Cytosolic PCNA interacts with S100A8 and controls an inflammatory subset of neutrophils in COVID-19

Formiga, Rodrigo de Oliveira; Pesenti, Lucie; Ladjemi, Maha Zohra; Andrieu, Muriel; Many, Souganya; Karunanithy, Vaarany; Bailly, Karine; Dhôte, Théo; Starick, Márick R; Rocha, Edroaldo Lummertz da; Lombardi, Emilia Puig; Frachet, Philippe; Granger, Vanessa; Chaisemartin, Luc de; Chollet‐Martin, Sylvie; Mouthon, Luc; Spiller, Fernando; Hurtado-Nédelec, Margarita; Martin, Clémence; Pène, Frédéric; Burgel, Pierre‐Régis; Tourneur, Léa; Witko‐Sarsat, Véronique

doi:10.1101/2022.10.12.22280984

Cited by 2 publications

(1 citation statement)

References 74 publications

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“…Additionally, a population of highly active, immunosuppressive neutrophils with a CD62L dim CD16 bright phenotype has recently been identified in COVID-19 and other inflammatory conditions [74][75][76][77] . In the L-ABBA-96, baricitinib dose-dependently reduced the proportion of IL-8-induced CD62L dim CD16 bright neutrophils in both unmigrated and migrated populations (Supplemental Figure 6).…”

Section: Figure 3 Baricitinib On the Endothelial Side Of The L-abba-9...mentioning

confidence: 99%

High Throughput Quantitation of Human Neutrophil Recruitment and Functional Responses in an Air-Blood Barrier Array

Viola,

Chen,

et al. 2024

Preprint

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Dysregulated neutrophil recruitment drives many pulmonary diseases, but most preclinical screening methods are unsuited to evaluate pulmonary neutrophilia, limiting progress towards therapeutics. Namely, high throughput therapeutic screening systems typically exclude critical neutrophilic pathophysiology, including blood-to-lung recruitment, dysfunctional activation, and resulting impacts on the air-blood barrier. To meet the conflicting demands of physiological complexity and high throughput, we developed an assay of 96-well Leukocyte recruitment in an Air-Blood Barrier Array (L-ABBA-96) that enables in vivo-like neutrophil recruitment compatible with downstream phenotyping by automated flow cytometry. We modeled acute respiratory distress syndrome (ARDS) with neutrophil recruitment to 20 ng/mL epithelial-side interleukin 8 (IL-8) and found a dose dependent reduction in recruitment with physiologic doses of baricitinib, a JAK1/2 inhibitor recently FDA-approved for severe COVID-19 ARDS. Additionally, neutrophil recruitment to patient-derived cystic fibrosis sputum supernatant induced disease-mimetic recruitment and activation of healthy donor neutrophils and upregulated endothelial e-selectin. Compared to 24-well assays, the L-ABBA-96 reduces required patient sample volumes by 25 times per well and quadruples throughput per plate. Compared to microfluidic assays, the L-ABBA-96 recruits two orders of magnitude more neutrophils per well, enabling downstream flow cytometry and other standard biochemical assays. This novel pairing of high-throughput in vitro modeling of organ-level lung function with parallel high-throughput leukocyte phenotyping substantially advances opportunities for pathophysiological studies, personalized medicine, and drug testing applications.

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Section: Figure 3 Baricitinib On the Endothelial Side Of The L-abba-9...mentioning

confidence: 99%

High Throughput Quantitation of Human Neutrophil Recruitment and Functional Responses in an Air-Blood Barrier Array

Viola,

Chen,

et al. 2024

Preprint

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Proliferating Cell Nuclear Antigen in the Era of Oncolytic Virotherapy

Kwan,

Mcdermott-Brown,

Muthana

2024

Viruses

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Proliferating cell nuclear antigen (PCNA) is a well-documented accessory protein of DNA repair and replication. It belongs to the sliding clamp family of proteins that encircle DNA and acts as a mobile docking platform for interacting proteins to mount and perform their metabolic tasks. PCNA presence is ubiquitous to all cells, and when located in the nucleus it plays a role in DNA replication and repair, cell cycle control and apoptosis in proliferating cells. It also plays a crucial role in the infectivity of some viruses, such as herpes simplex viruses (HSVs). However, more recently it has been found in the cytoplasm of immune cells such as neutrophils and macrophages where it has been shown to be involved in the development of a pro-inflammatory state. PCNA is also expressed on the surface of certain cancer cells and can play a role in preventing immune cells from killing tumours, as well as being associated with cancer virulence. Given the growing interest in oncolytic viruses (OVs) as a novel cancer therapeutic, this review considers the role of PCNA in healthy, cancerous, and immune cells to gain an understanding of how PCNA targeted therapy and oncolytic virotherapy may interact in the future.

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Cytosolic PCNA interacts with S100A8 and controls an inflammatory subset of neutrophils in COVID-19

Cited by 2 publications

References 74 publications

High Throughput Quantitation of Human Neutrophil Recruitment and Functional Responses in an Air-Blood Barrier Array

High Throughput Quantitation of Human Neutrophil Recruitment and Functional Responses in an Air-Blood Barrier Array

Proliferating Cell Nuclear Antigen in the Era of Oncolytic Virotherapy

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