For many years my research has focused on inflammation mediated by T helper type 2 (Th2) cells, often referred to as type-2 immunity. Th2 cells orchestrate complex cellular processes that mediate protective immunity against helminthic parasites or provoke destructive inflammation in response to ‘innocuous’ antigens termed allergens. Signaling elicited by Th2-derived cytokines involves the Jak/STAT signaling pathway, through which the STAT6 transcription factor plays a key role in regulating type-2 inflammation.
We showed that STAT6 induced by interleukin (IL)-4 acts as both a transcriptional activator and a negative regulator of target gene expression, indicating that STAT6 contributes to Th2 inflammation in different ways. In addition, we discovered that Suppressor of cytokine signaling (SOCS)1 is a novel IL-4/STAT6 target gene involved in the suppression of IL-4-dependent chemokine expression, which comports with the concept that SOCS proteins are classical negative feedback regulators. However, our recent studies provide evidence that SOCS2 is central to the control of TLR/NLR-dependent activation of dendritic cells (DCs) as well. This strongly supports an emerging model in which SOCS proteins function not only as feedback inhibitors of cytokine signaling, but also as regulators of pathways beyond cytokine-induced Jak/STAT signaling.