Suppressor of Cytokine Signaling 1 Regulates Embryonic Myelopoiesis Independently of Its Effects on T Cell Development

Abstract

Suppressor of cytokine signaling 1 (SOCS1) has been shown to play important roles in the immune system. It acts as a key negative regulator of signaling via receptors for IFNs and other cytokines controlling T cell development, as well as Toll receptor signaling in macrophages and other immune cells. To gain further insight into SOCS1, we have identified and characterized the zebrafish socs1 gene, which exhibited sequence and functional conservation with its mammalian counterparts. Initially maternally derived, the socs1 gene showed early zygotic expression in mesodermal structures, including the posterior intermediate cell mass, a site of primitive hematopoiesis. At later time points, expression was seen in a broad anterior domain, liver, notochord, and intersegmental vesicles. Morpholino-mediated knockdown of socs1 resulted in perturbation of specific hematopoietic populations prior to the commencement of lymphopoiesis, ruling out T cell involvement. However, socs1 knockdown also lead to a reduction in the size of the developing thymus later in embryogenesis. Zebrafish SOCS1 was shown to be able to interact with both zebrafish Jak2a and Stat5.1 in vitro and in vivo. These studies demonstrate a conserved role for SOCS1 in T cell development and suggest a novel T cell-independent function in embryonic myelopoiesis mediated, at least in part, via its effects on receptors using the Jak2–Stat5 pathway.

Depletion of suppressor of cytokine signaling-1a causes hepatic steatosis and insulin resistance in zebrafish

“…2A). It has been suggested that zebrafish SOCS1a plays a regulatory role in erythropoiesis and inflammatory gene expression (30,33). Consistent with this notion, obviously elevated levels of erythropoiesis have been found in socs1a-deficient fish during the early stages, as determined through an assay of gata1 expression at the 24-hpf stage (Fig.…”

“…The zebrafish SOCS1a has been suggested to play roles in hematopoiesis and the IFN signaling pathway similar to those of its mammalian counterpart. It has been demonstrated that the functions of SOCS1a could be mediated by the JAK2-STAT5 pathway (30,33). The results of this study demonstrated elevated levels of phosphorylated STAT5 and hemoglobin mediated via JAK activation in socs1a-null zebrafish compared with the wild-type control fish during their early and adult stages, which confirmed the roles of SOCS1a in activation of the JAK-STAT5 pathway and hematopoiesis (Fig.…”

“…The riboprobe of zebrafish gata1 was described previously (33). Antisense RNA probes labeled with digoxigenin-UTP (Roche) were synthesized and used for wholemount in situ hybridization, as described previously (27).…”

Regulation of Embryonic Hematopoiesis by a Cytokine-Inducible SH2 Domain Homolog in Zebrafish

“…This is particularly likely for the ortholog of SOCS1, which has been previously shown to regulate mammalian EPOR signaling (2), and the paralogs of SOCS3, which has been demonstrated to be a key in vivo regulator of G-CSFR (64). Indeed, we have previously demonstrated that zebrafish socs1 functions during embryonic hematopoiesis (65). Other mechanisms that may contribute to this transient phenotype remain to be determined, and the role of the cish.b paralog awaits further study.…”

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

“…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).…”