Functional characterization of three fish-specific interleukin-23 isoforms as regulators of Th17 signature cytokine expression in grass carp head kidney leukocytes

Yin, Licheng; Ren, Jiaqi; Wang, Dan; Feng, Shiyu; Qiu, Xinyang; Lv, Mingqi; Wang, Xinyan; Zhou, Hong

doi:10.1016/j.fsi.2019.06.028

Cited by 11 publications

(3 citation statements)

References 27 publications

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“…Last, we used the endotoxin removal agarose resin (20518ES10, Yeasen, China) to remove the endotoxin. 75 , 76 After balancing the agarose resin by TBS, the purified protein was loaded on the resin at the speed of 0.25 mL/min. The elution was collected for concentration and application in electrophysiology recording, macrophage cell immunity experiments and animal model.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

et al. 2021

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Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.

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Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

et al. 2021

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“…Furthermore, in mammals also IL‐23 induces a polarization of Th17 cell population with a unique inflammatory gene signature that includes IL‐17, IL‐6, TNF, CCL20, CCL22, IL1R1 and IL23R 70 . Recently, Yin and co‐workers 71 confirmed also for fish that recombinant IL‐23 is able to enhance the mRNA levels of IL‐17A/F1 and its secretion from head kidney leucocytes. Interestingly, our WGCN analysis indicated existence of the positive correlation between worm burden and expression of genes involved in inflammation and Th17‐response such as IL‐23 in the samples from head skin of guppies.…”

Section: Discussionmentioning

confidence: 95%

RNA‐Seq analysis of the guppy immune response against Gyrodactylus bullatarudis infection

Konczal

Ellison

Phillips

et al. 2020

Parasite Immunology

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Fish ectoparasites are an important selective agent in natural fish populations 1-4 and a major pest in commercial aquaculture. 5 Monogenean worms of the genus Gyrodactylus cause skin and/or gill damage that can result in severe pathology and host death. 6 This causes major problems in aquaculture and the ornamental fish trade (reviewed by Bakke et al 7). Gyrodactylids have also served as a model for host-parasite dynamics in ecological, evolutionary and epidemiological research, in laboratory, mesocosm and natural scenarios. 1,8-11 Despite the commercial importance and research value of gyrodactylids, understanding of the associated host immune responses is fragmentary. Previously, Buchmann 12 demonstrated that the complement system in rainbow trout (Oncorhynchus mykiss) can have a

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“…In mammals, it is well known that as a hallmark cytokine of the Th17 cell, IL-17 production is mainly manipulated by IL-23 through STAT3/RORγt signaling pathways ( 51 , 52 ). In teleosts, our previous study has proved that grass carp Il-23 isoforms also display the ability to trigger Th17-like response by Stat3 signaling ( 53 ). In this study, our results suggested that rgcIl-12 isoforms possessed a similar function to Il-23, and this notion was supported by the analysis of the signaling mechanisms that rgcIl-12BB up-regulated il-17a/f1 transcription through Stat3/Rorγt pathways in lymphocytes ( Figure 8 ).…”

Section: Discussionmentioning

confidence: 99%

Stimulus-Specific Expression, Selective Generation and Novel Function of Grass Carp (Ctenopharyngodon idella) IL-12 Isoforms: New Insights Into the Heterodimeric Cytokines in Teleosts

et al. 2021

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Interleukin-12 (IL-12) is a heterodimeric cytokine composed of a p35 subunit specific to IL-12 and a p40 subunit shared with IL-23. In this study, we unveiled the existence of two p35 paralogues in grass carp (named gcp35a and gcp35b). Notably, gcp35a and gcp35b displayed distinct inducible expression patterns, as poly I:C merely induced the gene expression of gcp35a but not gcp35b, while recombinant grass carp interferon-gamma (rgcIfn-γ) only enhanced the transcription of gcp35b but not gcp35a. Moreover, the signaling mechanisms responsible for the inducible expression of gcp35a and gcp35b mRNA were elucidated. Because of the existence of three grass carp p40 genes (gcp40a, gcp40b and gcp40c) and two p35 paralogues, six gcIl-12 isoforms were predicted by 3D modeling. Results showed that gcp40a and gcp40b but not gcp40c had the potential for forming heterodimers with both gcp35 paralogues via the disulfide bonds. Non-reducing electrophoresis experiments further disclosed that only gcp40b but not gcp40a or gcp40c could form heterodimers with gcp35 to produce secretory heterodimeric gcp35a/gcp40b (gcIl-12AB) and gcp35b/gcp40b (gcIl-12BB), which prompted us to prepare their recombinant proteins. These two recombinant proteins exhibited their extensive regulation on Ifn-γ production in various immune cells. Intriguingly, both gcIl-12 isoforms significantly enhanced the transcription of il-17a/f1 and il-22 in lymphocytes, and their regulation on il-17a/f1 expression was mediated by Stat3/Rorγt signaling, supporting the potential of gcIl-12 isoforms for inducing Th17-like responses. Additionally, stimulatory effects of gcIl-12 isoforms on il-17a/f1 and ifn-γ expression were attenuated by gcTgf-β1 via suppressing the activation of Stat3 signaling, implying that their signaling could be manipulated. In brief, our works provide new insights into the inducible expression pattern, heterodimeric generation and functional novelty of Il-12 isoforms in teleosts.

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Functional characterization of three fish-specific interleukin-23 isoforms as regulators of Th17 signature cytokine expression in grass carp head kidney leukocytes

Cited by 11 publications

References 27 publications

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

RNA‐Seq analysis of the guppy immune response against Gyrodactylus bullatarudis infection

Stimulus-Specific Expression, Selective Generation and Novel Function of Grass Carp (Ctenopharyngodon idella) IL-12 Isoforms: New Insights Into the Heterodimeric Cytokines in Teleosts

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