IL-12 superfamily members guiding the function of Rorγt-dependent innate lymphocytes
- Burkhard Becher1
© Becher; licensee BioMed Central Ltd. 2012
Published: 28 November 2012
Most MHC class II expressing Ag-presenting cells (APCs) have the capacity to produce the cytokines IL-12 and IL-23 . Both these heterodimeric pro-inflammatory cytokines share a common subunit (p40) which is covalently linked to p35 to form IL-12 and to p19 to form IL-23. The biology of these two related cytokines is extremely divers. IL-12 is best known for its capacity to polarize TH1 cells and to activate NK and NKT cells. IL-12 is thus primarily involved in the initiation of cellular immune responses agains intracellular pathogens. The biology of IL-23 is much less understood, but it becomes increasingly clear that IL-23 can activate innate lymphocytes including a subclass of γδ T cells  and Rorγt-dependent innate lymphocytes (ILCs) . IL-23 is further critical for the development of self-reactive pathogenic αβ helper T cells in various models of autoimmune diseases .
In the context of anti-tumor immunity we discovered that IL-23 plays only a minor role in the development of anti-tumor responses. In fact, we found IL-23 to have primarily tumor-supportive properties. In contrast, IL-12 has clearly a potent tumor-suppressive properties. Surprisingly, we identified a Rorγt-dependent IL-12R bearing ILC homing into the microenvironment of skin tumors . These ILCs upon sensing IL-12 are able to mount a potent innate response in the tumor-microenvironment, leading to alterations in tumor microvessels and the formation of a pro-inflammatory myeloid cell response. Taken together, our initial understanding of IL-12 and IL-23 biology was restricted to adaptive T cells. The impact of these cytokines on γδ T cells and ILCs is only now being discovered.
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