Clinical Relevance of Natural Killer Cells Following Hematopoietic Stem Cell Transplantation

Natural killer (NK) cells are one of the first cells to recover following allogeneic hematopoietic stem cell transplantation (HSCT), and are believed to play an important role in facilitating engraftment or preventing post-transplant infection and tumor recurrence. Recent studies have provided novel insights into the mechanisms by which NK cells mediate these highly clinically relevant immunological functions. In particular, the ability of NK cells to reduce the risk of graft versus host disease (GVHD) and increase the graft versus leukemia effect (GVL) in the setting of human leukocyte antigen (HLA)-haploidentical HSCT highlights their clinical potentials. NK cells also mediate anti-viral protection, in particular against cytomegalovirus (CMV), an infection that causes significant morbidity and mortality following transplant. Another crucial function of NK cells is providing protection against bacterial infections at the mucosal barriers. NK cells achieve this by promoting anti-microbial defenses and regeneration of epithelial cells. These recent exciting findings provide a strong basis for the formulation of novel NK cell-based immunotherapies. In this review, we summarize the recent advances related to the mechanisms, functions, and future clinical prospects of NK cells that can impact post-transplant outcomes.</p

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

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 (ROR&#947;t) 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 ROR&#947;t. 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.</p