Interleukin 17 is not required for autoimmune-mediated pathologic damage during chronic graft-versus-host disease.
The transition from acute to chronic graft-versus-host disease (aGVHD, cGVHD) is characterized by the progressive loss of self-tolerance and the development of autoimmune manifestations. Interleukin 17 (IL-17) is a proinflammatory cytokine that has been shown to play a prominent role in autoimmune disorders in the nontransplant setting, but the extent to which IL-17 is necessary for the autoimmunity that occurs as a consequence of GVHD is not known. In this study, we demonstrate using a combination of antibody-based and genetic approaches that IL-17 is not required for the loss of self-tolerance and resulting CD4(+)T cell-dependent pathologic damage that occurs during the evolution from aGVHD to cGVHD. Rather, T(H)1 cells and other proinflammatory cytokines are fully competent to promote autoimmune-mediated tissue damage. Thus, the selective targeting of IL-17 may not be a viable clinical strategy for preventing the autoimmune manifestations that develop during cGVHD.
Chen
Xiao
X
Bone Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Das
Rupali
R
Komorowski
Richard
R
van Snick
Jacques
J
Uyttenhove
Catherine
C
Drobyski
William R
WR
D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood / Q000503:physiopathology*; D016026:Bone Marrow Transplantation; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002678:Chimera / Q000378:metabolism; D002908:Chronic Disease; D003106:Colon / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000473:pathology; D009928:Organ Specificity; D015398:Signal Transduction
D016207:Cytokines; D020381:Interleukin-17