Methods of use for il-22 in the treatment of gastrointestinal graft vs. host disease

Abstract

The present invention provides methods and compositions for the use of IL-22 for treating conditions of intestinal injury and inflammatory conditions such as graft vs. host disease. Specifically, IL-22 can be used to increase Intestinal Stem Cell (ISC) recovery and for enhancing immune reconstitution following allogeneic hematopoietic transplantation. In particularly preferred embodiments, the present invention provides methods of using therapeutic IL-22, including a dimeric form of IL-22, in therapeutic compositions for treating graft vs. host disease, including hepatic, thymic, gastrointestinal, or other graft vs. host disease in hematopoietic stem cell transplant patients and in patients with inflammatory intestinal conditions.

1 . A method to promote the recovery/regeneration of gastrointestinal (GI) epithelial cells in a subject following injury or damage to the gastrointestinal tract, the method comprising contacting intestinal stem cells (ISC) of the subject with interleukin-22 (IL-22). 
     
     
         2 . A method for treating graft versus host disease (GVHD) in a subject without immunosupression, the method comprising administering to the subject a therapeutically effective amount of IL-22. 
     
     
         3 . A method for enhancing the proliferation of intestinal stem cells (ISC), the method comprising contacting said ISC with exogenous IL-22 under conditions to promote growth of ISC. 
     
     
         4 . The method of  claim 1 , wherein said IL-22 is recombinant IL-22. 
     
     
         5 . The method of  claim 4 , wherein said recombinant IL-22 is human IL-22. 
     
     
         6 . The method of  claim 1 , wherein IL-22 is in the form of an IL-22 dimer. 
     
     
         7 . The method of  claim 1 , wherein the IL-22 is in the form of a fusion protein. 
     
     
         8 . The method of  claim 1 , wherein the ISC are Lgr5+. 
     
     
         9 . The method of  claim 1 , wherein the injury or damage is due to inflammatory intestinal disease, inflammatory bowel disease, autoimmune disease, radiation or graft versus host disease (GVHD). 
     
     
         10 . The method of  claim 2 , wherein said therapeutically effective amount of IL-22 is administered to the subject before transplant. 
     
     
         11 . The method of  claim 2 , wherein said therapeutically effective amount of IL-22 is administered to the subject once onset of symptoms associated with injury to the GI tract is observed. 
     
     
         12 . The method of  claim 2 , wherein said therapeutically effective amount of IL-22 is administered to the subject from 1 day to 6 months following transplant. 
     
     
         13 . The method of  claim 2 , wherein said therapeutically effective amount of IL-22 is administered to the subject beginning from 1 week to 4 months following transplant. 
     
     
         14 . The method of  claim 2 , wherein said IL-22 is administered daily. 
     
     
         15 . The method of  claim 3 , wherein said contacting is in vivo or in vitro. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled)