IL-4, IL-13 and IFN-γ -induced genes in highly purified human neutrophils

Kummola, Laura; Salomaa, Tanja; Ortutay, Zsuzsanna; Savan, Ram; Young, Howard A.; Junttila, Ilkka

doi:10.1016/j.cyto.2023.156159

Cited by 3 publications

(1 citation statement)

References 83 publications

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“…Worthy of note, IFN-g priming led to the upregulation of FcgRI and TLR8 (potentially involved in IC-mediated signaling and HIV-1 sensing, respectively). Interestingly, this observation is in agreement with the recent study by Kumola et al, showing an upregulation of CD64 and TLR8 upon IFN-g stimulation as well as an enhanced expression of PD-L1 (52). This suggests that the enhanced expression of CD64 and PD-L1 we observed on the neutrophils from PLWH could be due to IFN-g-priming in vivo.…”

Section: Discussionsupporting

confidence: 94%

Enhanced Fc Receptor expression and distinct immunomodulatory properties of neutrophils during HIV-1 infection and therapy

Marsile-Medun,

Souchard,

Abba Moussa

et al. 2024

Preprint

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Neutrophils are innate immune cells that display immunomodulatory properties by secreting cytokines and chemokines. By using a mouse model of retroviral infection, we previously uncovered the key immunomodulatory function of neutrophils in promoting protective immunity during antiviral antibody therapy which occurs in a Fc-dependent manner. Here, we investigated the immunomodulatory properties of neutrophils in the context of HIV-1 infection and therapy. We characterized the functional activation and the modulation of Fcγ receptors (FcγRs) expression on neutrophils isolated from healthy donors (HD) or people living with HIV-1 (PLWH) upon stimulation with virions, free or in the form of immune complexes (ICs) made with broadly neutralizing antibodies (bNAbs). Neutrophils from HD secreted cytokines/chemokines in small amount upon activation by either stimulus. Interestingly, conditioning of neutrophils from HD with pro-inflammatory cytokines enhanced their cytokine/chemokine production upon activation by HIV-1 and ICs, highlighting that the inflammatory environment is key for neutrophils to show a functional response to these stimuli. Noteworthy, under inflammatory conditions, IC-activated neutrophils showed higher secretion of CXCL1 and CCL4 than HIV-1-stimulated neutrophils. Importantly, neutrophils from PLWH on antiretroviral treatment (ART) maintained their cytokine/chemokine secretion abilities when stimulated by TLR agonists, TNFα; or HIV-1/ICs. However, they displayed different phenotypic features as compared with neutrophils isolated from HD, notably higher expression of FcγRs. Our study provides new insights into the immunomodulatory properties of neutrophils during HIV-1 infection and therapy. This might contribute to the improvement of antiviral antibody therapies through the use of therapeutic approaches exploiting the immunomodulatory properties of these cells.

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Section: Discussionsupporting

confidence: 94%

Enhanced Fc Receptor expression and distinct immunomodulatory properties of neutrophils during HIV-1 infection and therapy

Marsile-Medun,

Souchard,

Abba Moussa

et al. 2024

Preprint

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SenMayo transcriptomic senescence panel highlights glial cells in the ageing mouse and human retina

Suresh,

Karthik,

Ouyang

et al. 2024

npj Aging

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There is a growing need to better characterise senescent cells in the CNS and retina. The recently published SenMayo gene panel was developed to identify transcriptomic signatures of senescence across multiple organ systems, but the retina was not included. While other approaches have identified senescent signatures in the retina, these have largely focused on experimental models in young animals. We therefore conducted a detailed single-cell RNA-seq analysis to identify senescent cell populations in the retina of different aged mice and compared these with five comprehensive human and mouse retina and brain transcriptome datasets. Transcriptomic signatures of senescence were most apparent in mouse and human retinal glial cells, with IL4, 13 and 10 and the AP1 pathway being the most prominent markers involved. Similar levels of transcriptional senescence were observed in the retinal glia of young and old mice, whereas the human retina showed significantly increased enrichment scores with advancing age.

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Stretched Vascular Endothelial Cells Polarized Neutrophils to N2 Type via TRPC1‐IL13‐STAT3 Axis

Jiang,

Chen,

Ouyang

et al. 2024

Oral Diseases

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ObjectiveVECs play a crucial role in regulating the function of neutrophils, which is essential for immune responses and inflammation. As stretch‐sensitive cells, VECs sense mechanical stretch through surface mechanoreceptors, converting external mechanical stimuli into biochemical signals. This study aimed to explore the molecular mechanisms underlying the regulation of neutrophil behavior by stretched VECs.Materials and MethodsThe key cytokine‐inducing neutrophil N2 polarization in the conditioned medium from stretched vascular endothelial cells (CM‐stretch) was validated through multifactorial matrix and flow cytometry. Additionally, the molecular mechanism underlying the response of vascular endothelial cells to stretch was systematically verified through layer‐by‐layer analysis using WB.ResultsIL13, not IL4, was ultimately identified as a key cytokine‐inducing neutrophil N2 polarization in CM‐stretch. Inhibition of the transient receptor potential channel (TRPC1) and siRNA‐mediated knockdown of TRPC1 both significantly decreased IL13 production. Furthermore, neutralizing IL13 in the CM‐stretch or inhibiting STAT3 phosphorylation inhibited neutrophil N2 polarization, as evidenced by reduced CD206 and VEGFA expression.ConclusionsThese results demonstrate that stretched VECs initiate a signaling cascade that induces neutrophil N2 polarization through the TRPC1‐IL13‐STAT3 axis, suggesting that mechanical stretching of VECs could shift neutrophil function from a pro‐inflammatory to a more regulatory and healing role.

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IL-4, IL-13 and IFN-γ -induced genes in highly purified human neutrophils

Cited by 3 publications

References 83 publications

Enhanced Fc Receptor expression and distinct immunomodulatory properties of neutrophils during HIV-1 infection and therapy

Enhanced Fc Receptor expression and distinct immunomodulatory properties of neutrophils during HIV-1 infection and therapy

SenMayo transcriptomic senescence panel highlights glial cells in the ageing mouse and human retina

Stretched Vascular Endothelial Cells Polarized Neutrophils to N2 Type via TRPC1‐IL13‐STAT3 Axis

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