IL-27p28 is essential for parent-to-F1 acute graft-versus-host disease.
Acute graft versus host disease (aGVHD) remains a life-threatening complication of bone marrow transplantation. Here we show that IL-27, a member of the IL-12 cytokine family, plays an essential role in a parent-to-F1 murine aGVHD model, using B6 mice as parents and B6D2 mice as F1 recipients. IL-27 is transiently detectable in the serum of B6D2 recipients of B6 spleen cells, with a peak at day 10. Treatment with anti-IL-27p28 mAb MM27.7B1 (αp28Ab), at the time of and six days after B6 cell transfer, blocked GVHD. Protection was associated with host cell survival and undiminished engraftment of donor cells, lack of host B-cell depletion, increased Th2-type immunoglobulin production, a decrease in serum IFN-γ, a drop in anti-H-2D(d) cytotoxic T lymphocyte activity and an increase in Foxp3(+) T cells. We therefore conclude that IL-27 plays a critical role in the parent-to-F1 model of aGVHD and that blocking IL-27 could have therapeutic relevance.
Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Reece G
RG
Marillier
Catherine
C
Uyttenhove
Stanislas
S
Goriely
Etienne
E
Marbaix
Jacques
J
Van Snick
D000208:Acute Disease; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology*; D007371:Interferon-gamma / Q000502:physiology; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D015431:Weight Loss
C486767:Il27 protein, mouse; D007378:Interleukins; D007371:Interferon-gamma
Cytotoxic; IFN-γ; IL-27; T lymphocyte; Treg cell; aGVHD