期刊
IMMUNITY
卷 37, 期 2, 页码 339-350出版社
CELL PRESS
DOI: 10.1016/j.immuni.2012.05.028
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资金
- National Institutes of Health [R01-HL069929, R01-CA107096, R01-AI080455, R01-AI 34495, R01-HL56067, K08-KHL115355A]
- American Society of Hematology
- American Society for Blood and Marrow Transplantation/Celgene
- AACR Judah Folkman Fellowship for Angiogenesis Research [10-40-18-GHOS]
- US Department of Defense: USAMRAA [W81XWH-09-1-0294]
- Radiation Effects Research Foundation (RERF-NIAID)
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center
- Lymphoma Foundation
- Alex's Lemonade Stand
- Geoffrey Beene Cancer Research Center at Memorial Sloan-Kettering Cancer Center
- Peter Solomon Fund
- Memorial Sloan-Kettering Cancer Center [NCI P30-CA008748]
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 pre-transplant 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.
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