SOCS genes: Critical regulators of cytokine signaling and immune responses

Immune and inflammatory systems are controlled by multiple cytokines, including interleukins (ILs) and interferons. Many of these cytokines exert their biological functions through Janus tyrosine kinases (JAKs) and STAT transcription factors. The CIS (cytokine-inducible SH2 protein) and SOCS (suppressors of cytokine signaling) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine-mediated homeostasis, including innate and adaptive immunity. We investigated the roles of suppressors of cytokine signaling (SOCSs) in regulating dendritic cell (DC) maturation and function. We showed that SOCS1-deficient DCs induced stronger Th1-type responses both in vitro and in vivo. SOCS1-deficient DCs induced higher interferon-γ (IFNγ) production from naive T cells than wild-type DCs in vitro. Lymph node T cells also produced higher amount of IFNγ when SOCS1-deficient bone marrow-derived (BM) DCs were transferred in vivo. Moreover, SOCS1−/− BMDCs raised more effective anti-tumor immunity than wild-type BMDCs. On the other hand, SOCS3-deficeint BMDCs expressed lower levels of MHC, co-stimulators and CD40 in response to LPS. SOCS3-deficient DCs induced lower T cell responses. Thus, SOCS1 and SOCS3 reciprocally regulate DC maturation.