Oxidized ATP inhibits T-cell-mediated autoimmunity.
T cells directed against self antigens play an important role in several autoimmune diseases. The available immunosuppressive compounds used to treat autoimmune diseases are limited, and often they have side effects that limit their application. T cells express ATP receptors, which could be new target molecules to treat autoimmune disease. Here we analyzed the effect of oxidized ATP (oxATP), an inhibitor of the ATP receptor P2rx7, in different murine models of T-cell-mediated autoimmune diseases. Treatment with oxATP inhibited proliferation and effector function of T cells. In the systems we used, oxATP did not obviously interfere with the innate immune response, but strongly reduced antigen-specific T-cell responses. This treatment ameliorated T-cell-mediated autoimmune type I diabetes and autoimmune encephalitis in mice. In conclusion, oxATP was found to strongly inhibit activated T cells and could thus be used to target T-cell-mediated autoimmune disease.
Lang
Philipp A
PA
Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, UHN, Toronto, ON, Canada. karlslang@gmail.com
Merkler
Doron
D
Funkner
Pauline
P
Shaabani
Namir
N
Meryk
Andreas
A
Krings
Caroline
C
Barthuber
Carmen
C
Recher
Mike
M
Brück
Wolfgang
W
Häussinger
Dieter
D
Ohashi
Pamela S
PS
Lang
Karl S
KS
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology
C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C017199:2',3'-dialdehyde ATP; D007371:Interferon-gamma; D000255:Adenosine Triphosphate