STAT3/SOCS3 axis contributes to the outcome of salmonid whirling disease

Abstract

There are differences in disease susceptibility to whirling disease (WD) among strains of rainbow trout. The North American strain Trout Lodge (TL) is highly susceptible, whereas the German Hofer (HO) strain is more resistant. The suppressor of cytokine signaling (SOCS) proteins are key in inhibiting cytokine signaling. Their role in modulating the immune response against whirling disease is not completely clear. This study aimed at investigating the transcriptional response of SOCS1 and SOCS3 genes to Myxobolus cerebralis along with that of several upstream regulators and immune response genes. M. cerebralis induced the expression of SOCS1, the IL-6-dependent SOCS3, the anti-inflammatory cytokine IL-10 and the Treg associated transcription factor FOXP3 in TL fish at multiple time points, which likely caused a restricted STAT1 and STAT3 activity affecting the Th17/Treg17 balance. The expression of SOCS1 and the IL-6-dependent SOCS3 was induced constraining the activation of STAT1 and STAT3 in TL fish, thereby causing Th17/Treg17 imbalance and leaving the fish unable to establish a protective immune response against M. cerebralis or control inflammatory reactions increasing susceptibility to WD. Conversely, in HO fish, the expression of SOCS1 and SOCS3 was restrained, whereas the expression of STAT1 and IL-23-mediated STAT3 was induced potentially enabling more controlled immune responses, accelerating parasite clearance and elevating resistance. The induced expression of STAT1 and IL-23-mediated STAT3 likely maintained a successful Th17/Treg17 balance and enabled fish to promote effective immune responses favouring resistance against WD. The results provide insights into the role of SOCS1 and SOCS3 in regulating the activation and magnitude of host immunity in rainbow trout, which may help us understand the mechanisms that underlie the variation in resistance to WD.

Transcriptome Analysis Revealed Potential Mechanisms of Resistance to Trichomoniasis gallinae Infection in Pigeon (Columba livia)

“…Findings of these investigations linked various immune-related genes and pathways with resistance to parasitic infection. Several genes previously linked to parasite resistance including ACAT2 ( 34 ), SOCS3 ( 35 – 37 ), and IGSF21 ( 38 ) also showed differential expression pattern between tolerant and susceptible birds. These genes are therefore promising candidates for further validation and practical application.…”

Butyric Acid Protects Against Renal Ischemia–Reperfusion Injury by Adjusting the Treg/Th17 Balance via HO-1/p-STAT3 Signaling

“…Our study found that the frequency of Th17 cells in the BA treatment group was significantly reduced, suggesting that BA regulates Treg/Th17 balance and regulates CD4 + T cell differentiation. Suppressor of cytokine signaling family (SOCS1/SOCS3) is necessary for the balance of Treg/Th17 population in different organ diseases ( Qu et al, 2017 ; Wang D. et al, 2018 ; Kmiolek et al, 2020 ; Saleh et al, 2020 ). Therefore, we detected the expression of RORγt, SOCS1, and SOCS3 expression.…”

Docosahexaenoic acid inhibits vascular smooth muscle cell migration and proliferation by decreasing microRNA‑155 expression levels

“…Identification of the target gene of microRNA-155 is important for understanding the biological functions of microRNA-155, and is required to investigate a possible mechanism of the regulatory effects of microRNA-155 on VSMC proliferation and migration. According to the target gene prediction data generated by TargetScan ( ), Socs1 was a candidate target based on a study in macrophages ( 28 ). Socs1 is a suppressor of cytokine signalling, which is required for cell growth and survival ( 28 ).…”

“…According to the target gene prediction data generated by TargetScan ( ), Socs1 was a candidate target based on a study in macrophages ( 28 ). Socs1 is a suppressor of cytokine signalling, which is required for cell growth and survival ( 28 ). The mRNA levels of Socs1 were significantly increased following transfection with the microRNA-155-mimics, compared with the control ( Fig.…”