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PMID: 22921121 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Immunity ·Vol. 37 ·No. 2 ·2012-08-24 ·Pages 339-50

Hanash AM, Dudakov JA, Hua G, O'Connor MH, Young LF, Singer NV, West ML, Jenq RR, Holland AM, Kappel LW, Ghosh A, Tsai JJ, Rao UK, Yim NL, Smith OM, Velardi E, Hawryluk EB, Murphy GF, Liu C, Fouser LA, Kolesnick R, Blazar BR, van den Brink MR

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.

MeSH Terms
Animals Bone Marrow Transplantation/adverse effects,immunology Disease Models, Animal Flow Cytometry Graft vs Host Disease/immunology,mortality Immunohistochemistry Interleukin-23/metabolism Interleukins/genetics,immunology,metabolism Intestine, Small/cytology,immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Receptors, Interleukin/metabolism Stem Cells/metabolism
Chemicals
Interleukin-23 Interleukins Receptors, Interleukin interleukin-22 receptor interleukin-22
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Hanash Alan M
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. hanasha@mskcc.org
Dudakov Jarrod A
Hua Guoqiang
O'Connor Margaret H
Young Lauren F
Singer Natalie V
West Mallory L
Jenq Robert R
Holland Amanda M
Kappel Lucy W
Ghosh Arnab
Tsai Jennifer J
Rao Uttam K
Yim Nury L
Smith Odette M
Velardi Enrico
Hawryluk Elena B
Murphy George F
Liu Chen
Fouser Lynette A
Kolesnick Richard
Blazar Bruce R
van den Brink Marcel R M
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2012.05.028
Email
hanasha@mskcc.org
Published
2012-08-24
Pages
339-50
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3477611
Subset
IM
Grants
NCI NIH HHS · P01 CA023766 · United States
NIAID NIH HHS · R01 AI080455 · United States
NIAID NIH HHS · R01 AI034495 · United States
NHLBI NIH HHS · R01-HL069929 · United States
NCI NIH HHS · R01-CA107096 · United States
NHLBI NIH HHS · K08 HL115355 · United States
NCI NIH HHS · P01 CA142106 · United States
NIAID NIH HHS · R01-AI080455 · United States
NIAID NIH HHS · R01-AI 34495 · United States
NHLBI NIH HHS · R01 HL069929 · United States
NCATS NIH HHS · UL1 TR000064 · United States
NIAID NIH HHS · P01 AI056299 · United States
NCI NIH HHS · R01 CA107096 · United States
NCI NIH HHS · P30 CA008748 · United States
NHLBI NIH HHS · R01-HL56067 · United States
NHLBI NIH HHS · R01 HL056067 · United States
NCI NIH HHS · P30-CA008748 · United States
PHS HHS · K08-KHL115355A · United States
NCI NIH HHS · R01 CA072669 · United States
Corrections
CommentIn
PMID: 22921117
External Links
PubMed source DOI: 10.1016/j.immuni.2012.05.028 PMC Full Text View journal details
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