J Cancer 2013; 4(1):57-65. doi:10.7150/jca.5048
IL-22: An Evolutionary Missing-Link Authenticating the Role of the Immune System in Tissue Regeneration
1. Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA.
2. Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA;
3. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA;
4. Department of Microbiology/Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kumar P, Rajasekaran K, Palmer JM, Thakar MS, Malarkannan S. IL-22: An Evolutionary Missing-Link Authenticating the Role of the Immune System in Tissue Regeneration. J Cancer 2013; 4(1):57-65. doi:10.7150/jca.5048. Available from http://www.jcancer.org/v04p0057.htm
Tissue regeneration is a critical component of organ maintenance. The ability of lymphocytes to kill pathogen-infected cells has been well-studied. However, the necessity for lymphocytes to participate in reconstruction of destroyed tissues has not been explored until recently. Interleukin (IL)-22, a newly defined cytokine exclusively produced by subsets of lymphocytes, provides the strongest proof yet for the tissue regenerative potentials of the immune system. IL-22 plays an obligatory role in epithelial homeostasis in the gut, liver and lung. The receptor for IL-22 (IL-22R1 and IL-10R2) is predominantly expressed by epithelial cells. While the pro-inflammatory effect is questioned, the pro-constructive potential of IL-22 is well established. It is evident from the response to IL-22, that epithelial cells not only produce anti-microbial peptides but also actively proliferate. Aryl hydrocarbon receptor (AhR) and retinoic acid-related orphan receptor (RORγt) transcription factor are required for IL-22 generation from Lymphoid Tissue inducer cells LTi, Th22 and NK-like cells. However, IL-22 production from conventional NK cells is independent of AhR and RORγt. In this review, we present a case for a paradigm shift in how we define the function of the immune system. This would include tissue regeneration as a legitimate immune function.
Keywords: Interleukin (IL)-22, immune function, tissue regeneration