Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease Journal Article


Authors: Hanash, A.; Dudakov, J.; Hua, G.; O'connor, M.; Young, L.; Singer, N.; West, M.; Jenq, R.; Holland, A.; Kappel, L.; Ghosh, A.; Tsai, J.; Rao, U.; Yim, N.; Smith, O.; Velardi, E.; Hawryluk, E. B.; Murphy, G.; Liu, C.; Fouser, L.; Kolesnick, R.; Blazar, B.; Van Den Brink, M.
Article Title: Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease
Abstract: Little is known about the maintenance of intestinal stem cells (ISCs) and progenitors during immune-mediated tissue damage or about the susceptibility of transplant recipients to tissue damage mediated by the donor immune system during graft versus host disease (GVHD). We demonstrate here that deficiency of recipient-derived IL-22 increased acute GVHD tissue damage and mortality, that ISCs were eliminated during GVHD, and that ISCs as well as their downstream progenitors expressed the IL-22 receptor. Intestinal IL-22 was produced after bone marrow transplant by IL-23-responsive innate lymphoid cells (ILCs) from the transplant recipients, and intestinal IL-22 increased in response to pretransplant conditioning. However, ILC frequency and IL-22 amounts were decreased by GVHD. Recipient IL-22 deficiency led to increased crypt apoptosis, depletion of ISCs, and loss of epithelial integrity. Our findings reveal IL-22 as a critical regulator of tissue sensitivity to GVHD and a protective factor for ISCs during inflammatory intestinal damage. © 2012 Elsevier Inc.
Keywords: immunohistochemistry; controlled study; protein expression; unclassified drug; mortality; nonhuman; flow cytometry; cd8+ t lymphocyte; animal cell; mouse; animals; mice; mice, knockout; animal tissue; apoptosis; animal experiment; animal model; inflammation; mice, inbred balb c; mice, inbred c57bl; b lymphocyte; stem cell; regulatory t lymphocyte; acute graft versus host disease; whole body radiation; donor; immune response; tumor necrosis factor alpha; gamma interferon; cd4+ t lymphocyte; stem cells; natural killer cell; radiosensitivity; cytokine production; disease models, animal; immunosuppressive treatment; bone marrow transplantation; graft vs host disease; intestine, small; cell protection; tissue injury; enteropathy; graft recipient; interleukin 22; interleukins; cytokine receptor; lymphoid cell; interleukin 23; crypt cell; intestine epithelium; interleukin 22 receptor; immune mediated injury; intestinal stem cell; interleukin-23; receptors, interleukin
Journal Title: Immunity
Volume: 37
Issue: 2
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2012-08-24
Start Page: 339
End Page: 350
Language: English
DOI: 10.1016/j.immuni.2012.05.028
PROVIDER: scopus
PUBMED: 22921121
PMCID: PMC3477611
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 1 October 2012" - "CODEN: IUNIE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Alan M Hanash
    81 Hanash
  2. Jarrod Andrew Dudakov
    58 Dudakov
  3. Robert R Jenq
    102 Jenq
  4. Richard N Kolesnick
    235 Kolesnick
  5. Guoqiang Hua
    16 Hua
  6. Jennifer Tsai
    44 Tsai
  7. Arnab Ghosh
    40 Ghosh
  8. Enrico Velardi
    44 Velardi
  9. Odette Marsinay Smith
    95 Smith
  10. Uttam Keshav Rao
    28 Rao
  11. Nury Yim
    25 Yim
  12. Amanda M Holland
    52 Holland
  13. Lauren Young
    39 Young
  14. Natalie Singer
    24 Singer
  15. Mallory Lia West
    24 West