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J Cancer 2013; 4(1):57-65. doi:10.7150/jca.5048 This issue Cite

Review

IL-22: An Evolutionary Missing-Link Authenticating the Role of the Immune System in Tissue Regeneration

Pawan Kumar¹, Kamalakannan Rajasekaran¹, Jeanne M Palmer^1,2, Monica S Thakar^1,3,✉, Subramaniam Malarkannan^1,2,4,✉

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.

✉ Corresponding author: Subramaniam Malarkannan (Subra.malaredu) or Thakar, Monica (mthakaredu).

Abstract

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

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