IL-1ß Induces SOCS2 Expression in Human Dendritic Cells.

ABSTRACT

Dendritic cells (DCs) regulate immunity and inflammation and respond to various stimuli, including cytokines. IL-1ß is a key cytokine in the course of both acute and chronic inflammatory responses, making it indispensable for protection of the host, but also linking it to several diseases. Thus, IL-1ß signaling must be tightly regulated. As suppressor of cytokine signaling (SOCS) proteins effectively control immune responses, we investigated the role of SOCS2 in IL-1ß-induced DC activation. Human monocyte-derived DCs were stimulated with IL-1ß, and SOCS2 mRNA and protein levels were measured. DC activation was assessed by cytokine secretion and surface marker expression. For functional analysis, small interfering RNA (siRNA)-based SOCS2 silencing was performed. SOCS2 expression was also analyzed in a curated NCBI GEO dataset of myeloid leukemia patients. We found IL-1ß to be a potent inducer of SOCS2 expression. By silencing SOCS2, we showed that SOCS2 specifically limits IL-1ß-induced IL-8 secretion. Moreover, our analysis revealed that SOCS2 levels are significantly increased in patients with acute and chronic myeloid leukemia, two hematological malignancies where disease progression is closely linked to IL-1ß. This study identifies SOCS2 as a novel IL-1ß-inducible target gene and points toward a potential role of SOCS2 in IL-1ß-mediated DC activation.