title: Controlling the burn and fueling the fire: defining the role for the alarmin interleukin-33 in alloimmunity.
abstract: OBJECTIVE
  The purpose of this review is to provide a general update on recent developments in the immunobiology of IL-33 and IL-33-targeted immune cells. We also discuss emerging concepts regarding the potential role IL-33 appears to play in altering alloimmune responses mediating host-versus-graft and graft-versus-host alloresponses.
  
  
  RESULTS
  Stromal cells and leukocytes display regulated expression of IL-33 and may actively or passively secrete this pleotropic cytokine. Type 2 innate lymphoid cells and a large proportion of tissue resident regulatory T cells (Treg) express membrane-bound suppressor of tumorigenicity 2 (ST2), the IL-33 receptor. Although Treg are appreciated suppressors of the inflammatory function of immune cells, both type 2 innate lymphoid cells and tissue resident Treg could play key roles in tissue repair and homeostasis. The functions of IL-33 in transplantation are poorly understood. However, like other disease models, the functions of IL-33 in alloimmunity appear to be quite pleiotropic. IL-33 is associated with immune regulation and graft protection in cardiac transplant settings. Yet, it is highly proinflammatory and stimulates lethal graft-versus-host disease through its capacity to stimulate type 1 immunity.
  
  
  CONCLUSIONS
  Intensive studies on IL-33/ST2 signaling pathways and ST2 cell populations in solid organ and cell transplantation are warranted. A better understanding of this important pathway will provide promising therapeutic targets controlling pathogenic alloimmune responses, as well as potentially facilitating the function of regulatory and reparative immune cells posttransplantation.
authors.affiliation: aThomas E. Starzl Transplantation Institute and Department of Surgery, Pittsburgh, Pennsylvania, USA bDepartment of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China cDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania , USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Heth R
authors.initials: HR
authors.lastname: Turnquist
mesh_terms: D000067531:Alarmins / Q000276:immunology*; D000818:Animals; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D000067596:Interleukin-33 / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D015398:Signal Transduction
chemical_list: D000067531:Alarmins; D000067596:Interleukin-33