Type 2 Innate Lymphoid Cells Treat and Prevent GI Tract GvHD Through Enhanced Accumulation of Myeloid Derived Suppressor Cells

Danny W Bruce, Heather E Stefanski, Benjamin G Vincent, Trisha A Dant, Shannon Reisdorf, Hemamalini Bommiasamy, David A Serody, Justin E Wilson, Karen P McKinnon, Warren D Shlomchik, Bruce R Blazar, Dietmar Zaiss, Andrew N J McKenzie, James M Coghill, Jonathan S Serody

Research output: Contribution to journalArticlepeer-review

Abstract

Acute graft-versus-host disease (aGvHD) is the most common complication for patients undergoing allogeneic stem cell transplantation. Despite extremely aggressive therapy targeting donor T cells, patients with grade III or greater aGvHD of the lower GI tract, who do not respond to therapy with corticosteroids, have a dismal prognosis. This has increased interest in the function of local immune and non-immune cells in regulating the inflammatory process in the GI tract during aGvHD. Here, we demonstrate using murine models of allogeneic bone marrow transplantation, that type 2 innate lymphoid cells (ILC2s) in the lower GI tract are sensitive to conditioning therapy and show very limited ability to repopulate from donor bone marrow. Infusion of donor ILC2s was effective in reducing the lethality of aGvHD and in treating lower GI tract disease. This was associated with reduced donor pro-inflammatory Th1 and Th17 cells, accumulation of donor myeloid derived suppressor cells (MDSCs) mediated by ILC2 production of IL-13, improved GI tract barrier function and a preserved graft-versus-leukemia (GvL) response. Infusion of donor ILC2s to restore gastrointestinal tract homeostasis may be critical for optimal treatment of severe lower GI tract aGvHD.
Original languageEnglish
JournalJournal of Clinical Investigation
Early online date4 Apr 2017
DOIs
Publication statusPublished - May 2017

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