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  • Invited speaker presentation
  • Open Access

IL-12 superfamily members guiding the function of Rorγt-dependent innate lymphocytes

  • 1
Journal of Translational Medicine201210 (Suppl 3) :I15

  • Published:


  • Cellular Immune Response
  • Intracellular Pathogen
  • Skin Tumor
  • Innate Response
  • Superfamily Member

Most MHC class II expressing Ag-presenting cells (APCs) have the capacity to produce the cytokines IL-12 and IL-23 [1]. 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 [2] and Rorγt-dependent innate lymphocytes (ILCs) [3]. IL-23 is further critical for the development of self-reactive pathogenic αβ helper T cells in various models of autoimmune diseases [4].

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 [5]. 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.

Authors’ Affiliations

Institute of Experimental Immunology, University of Zurich, Switzerland


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© Becher; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.