Fish Suppressors of Cytokine Signaling (SOCS): Gene Discovery, Modulation of Expression and Function

Abstract

The intracellular suppressors of cytokine signaling (SOCS) family members, including CISH and SOCS1 to 7 in mammals, are important regulators of cytokine signaling pathways. So far, the orthologues of all the eight mammalian SOCS members have been identified in fish, with several of them having multiple copies. Whilst fish CISH, SOCS3, and SOCS5 paralogues are possibly the result of the fish-specific whole genome duplication event, gene duplication or lineage-specific genome duplication may also contribute to some paralogues, as with the three trout SOCS2s and three zebrafish SOCS5s. Fish SOCS genes are broadly expressed and also show species-specific expression patterns. They can be upregulated by cytokines, such as IFN-γ, TNF-α, IL-1β, IL-6, and IL-21, by immune stimulants such as LPS, poly I:C, and PMA, as well as by viral, bacterial, and parasitic infections in member- and species-dependent manners. Initial functional studies demonstrate conserved mechanisms of fish SOCS action via JAK/STAT pathways.

A Review of Immune System Components, Cytokines, and Immunostimulants in Cultured Finfish Species

“…As a result of this regulatory mechanism, it is clear that negative feedback for the SOCS proteins is crucial to proper functioning of teleost immune systems, in addition to proper cytokine production. Aside from the negative inhibition, certain PAMPs, bacteria, viruses, and parasites have demonstrated the ability to induce SOCS expression [72]. Furthermore, the teleost stress response, more specifically the release of cortisol, has been found to up-regulate the expression of the SOCS genes and create an inhibition of the regulatory cytokines [73].…”

Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes

“…In recent years, SOCS proteins have been cloned in fish models, e.g., trout (Wang et al 2010, Maehr et al 2014, salmon (Skjesol et al 2014), catfish (Yao et al 2015), turbot (Zhang et al 2011), and zebrafish (Wang et al 2011). Data mining of genome databases not only reveals the orthologues of mammalian SOCS but also reveals new paralogues of Cish, Socs3, and Socs5 unique to fish species (Jin et al 2008, Wang et al 2011, which are presumably the result of fish-specific 3R genome duplication (Kassahn et al 2009).…”

Tissue-specific molecular immune response to lipopolysaccharide challenge in emaciated anadromous Arctic charr

“…The SOCS genes act as key negative-regulators of cytokine signalling. Homologues of all the mammalian SOCS family members including SOCS-1, SOCS-2 and SOCS-3, have been identified in fish (Wang et al, 2011), but a functional role has not been thoroughly described yet. Our results reveal for the first time that fasted Arctic charr increase the expression of SOCS genes in a tissue specific manner.…”

“…We recently showed the SOCS genes to be responsive to cortisol, the major stress hormone in fish, which highlights the role played by the SOCS genes in integrating different physiological responses (Philip et al, 2012). Additionally, it has also been shown that SOCS proteins interact with GH receptor signalling (Wang et al, 2011). Fish growth is a complex function mostly regulated by the growth hormone (GH)/insulin-like growth factor (IGF) system (Gabillard et al, 2006).…”

“…The negative regulation of cytokine signalling by SOCS involves activation of the JAK2-STAT5 pathway (O'Sullivan et al, 2011). Homologues of all the eight mammalian SOCS family members have been discovered in fish (Wang et al, 2011), while SOCS-1, SOCS-2 and SOCS-3 have been characterized in salmonids (Wang and Secombes, 2008). Although the functional significance of SOCS transcript abundance is unclear in fish, the mRNA abundance of SOCS-1-3 have been shown to be modulated by immunostimulants (Philip et al, 2012;Shepherd et al, 2012;Wang et al, 2011), but their expression with fasting is less clear.…”