Buy one, get one free: additional functions of GM-CSF in DC maturation

The hematopoietic growth factor GM-CSF has long been known for its colony-formation properties in the generation of neutrophils, macrophages and DCs. However, a study by Miah et al. in this issue of the European Journal of Immunology [Eur. J. Immunol. 2012. 42: 58-68] reports that GM-CSF also terminates its own proliferation-inducing STAT5-signaling via induction of the SOCS family member cytokine-inducible SH2-domain protein (CISH, also known as CIS). CISH levels were continuously increased during murine GM-CSF-dependent DC development in vitro and CISH, in turn, suppressed STAT5 phosphorylation to inhibit further GM-CSF signals. In addition, CISH activity promoted MHC class I- but not MHC class II-dependent antigen presentation after DC maturation, selectively supporting the priming of CTLs but not Th1 responses. This is the first demonstration of a molecular switch turning proliferating DC precursors into the differentiated immature DC stage and beyond, thereby paving the way for DC maturation. Since CISH polymorphisms critically affect human susceptibility to infectious diseases, further studies with this interesting molecule and its mutants will allow further insights into the induction of immune responses by DCs in humans.