Different Immunoregulation Roles of Activin A Compared With TGF-β

Li, Fanglin; Long, Yiru; Yu, Xiaolu; Tong, Yongliang; Gong, Likun

doi:10.3389/fimmu.2022.921366

Cited by 9 publications

(4 citation statements)

References 68 publications

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“…Innate immune cells, including neutrophils and macrophages, produce activin, which can signal in an autocrine/paracrine fashion to promote pro-inflammatory phenotypes of these cells 27 , 31 , 34 . Additionally, activin can signal along the MAPK and PI3K pathways.…”

Section: Resultsmentioning

confidence: 99%

Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis

Wiley,

Bauer,

Alvarez

et al. 2024

Sci Rep

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Acute Pancreatitis (AP) is associated with high mortality and current treatment options are limited to supportive care. We found that blockade of activin A (activin) in mice improves outcomes in two murine models of AP. To test the hypothesis that activin is produced early in response to pancreatitis and is maintained throughout disease progression to stimulate immune cells, we first performed digital spatial profiling (DSP) of human chronic pancreatitis (CP) patient tissue. Then, transwell migration assays using RAW264.7 mouse macrophages and qPCR analysis of “neutrophil-like” HL-60 cells were used for functional correlation. Immunofluorescence and western blots on cerulein-induced pancreatitis samples from pancreatic acinar cell-specific Kras knock-in (Ptf1aCreER™; LSL-KrasG12D) and functional WT Ptf1aCreER™ mouse lines mimicking AP and CP to allow for in vivo confirmation. Our data suggest activin promotes neutrophil and macrophage activation both in situ and in vitro, while pancreatic activin production is increased as early as 1 h in response to pancreatitis and is maintained throughout CP in vivo. Taken together, activin is produced early in response to pancreatitis and is maintained throughout disease progression to promote neutrophil and macrophage activation.

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Section: Resultsmentioning

confidence: 99%

Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis

Wiley,

Bauer,

Alvarez

et al. 2024

Sci Rep

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“…IL-6 is a pleiotropic cytokine, with many roles in inflammation and immune response [ 47 ]. Activin A encoded by INHBA is described as a T h 2 cytokine, as it is abundant in these cells, furthermore the neutralization of this cytokine in vivo significantly decreased IgE production in mice immunized with ovalbumin [ 48 ]. We have recently identified a cluster of patients with high levels of pro-inflammatory cytokines and IgE levels by mass cytometry [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Cytokine profiling and transcriptomics in mononuclear cells define immune variants in Meniere Disease

Flook,

Rojano,

Gallego-Martinez

et al. 2024

Genes Immun

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Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1β into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64 $$\times$$ × 10−6) and IGLV3-21 (p = 6.28 $$\times$$ × 10−3), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1β with up-regulation of IL6 (p = 7.65 $$\times$$ × 10−8) and INHBA (p = 3.39 $$\times$$ × 10−7) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8+ T cells.

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“…The activated ALK4 induces the activation and nuclear translocation of Smad protein and regulates the expression of target genes. 195 Activin A can inhibit DNA synthesis in hepatocytes in an autocrine manner during LR to exert its role as a negative regulator. 196 Recent studies have shown that activin A released by endothelial cells as a transcription target of Kruppel-like transcription factor 2 (KLF2) can negatively regulate hepatocyte proliferation and LR.…”

Section: Signaling Pathways In Lrmentioning

confidence: 99%

Signaling pathways of liver regeneration: Biological mechanisms and implications

Zhang,

Sun,

Zhao

et al. 2024

iScience

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Different Immunoregulation Roles of Activin A Compared With TGF-β

Cited by 9 publications

References 68 publications

Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis

Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis

Cytokine profiling and transcriptomics in mononuclear cells define immune variants in Meniere Disease

Signaling pathways of liver regeneration: Biological mechanisms and implications

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