Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease

被引：490

作者：

Hanash, Alan M. ^{[1
]}

Dudakov, Jarrod A. ^{[2
]}

Hua, Guoqiang ^{[3
]}

O'Connor, Margaret H. ^{[2
]}

Young, Lauren F. ^{[2
]}

Singer, Natalie V. ^{[2
]}

West, Mallory L. ^{[2
]}

Jenq, Robert R. ^{[1
]}

Holland, Amanda M. ^{[2
]}

Kappel, Lucy W. ^{[2
]}

Ghosh, Arnab ^{[2
]}

Tsai, Jennifer J. ^{[2
]}

Rao, Uttam K. ^{[2
]}

Yim, Nury L. ^{[2
]}

Smith, Odette M. ^{[2
]}

Velardi, Enrico ^{[2
]}

Hawryluk, Elena B. ^{[5
]}

Murphy, George F. ^{[5
]}

Liu, Chen ^{[6
]}

Fouser, Lynette A. ^{[7
]}

Kolesnick, Richard ^{[4
]}

Blazar, Bruce R. ^{[8
]}

van den Brink, Marcel R. M. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol, New York, NY 10065 USA

[5] Harvard Univ, Brigham & Womens Hosp, Program Dermatopathol, Sch Med, Boston, MA 02115 USA

[6] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA

[7] Pfizer Worldwide Res & Dev, Inflammat & Immunol Res Unit, Biotherapeut Res & Dev, Cambridge, MA 02140 USA

[8] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA

来源：

IMMUNITY | 2012年 / 37卷 / 02期

基金：

美国国家卫生研究院;

关键词：

INNATE LYMPHOID-CELLS; ALLOREACTIVE T-CELLS; MARROW-TRANSPLANTATION; TH17; CELLS; IL-22; EXPRESSION; INFLAMMATION; HOMEOSTASIS; COLITIS; MICE;

D O I：

10.1016/j.immuni.2012.05.028

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：339 / 350

页数：12

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