Identifying the cells breaching self-tolerance in autoimmunity.
Activation of auto-reactive T cells by activated dendritic cells (DCs) presenting self-Ag is widely assumed to be the precipitating event in the development of autoimmune disease. However, despite such widely held preconceptions, supporting data are scarce and subjective, particularly in experimental arthropathy. We have adapted a novel murine model of breach of self-tolerance allowing evaluation of the contribution of endogenous DCs to the development of autoimmune responses and disease. For the first time, we reveal the critical role played by conventional DCs, and the timing and location of this process. We further demonstrate the importance of this finding by clinically relevant, therapeutic manipulation of conventional DC function, resulting in decreased autoimmune phenotype and disease severity.
Benson
Robert A
RA
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom.
Patakas
Agapitos
A
Conigliaro
Paola
P
Rush
Catherine M
CM
Garside
Paul
P
McInnes
Iain B
IB
Brewer
James M
JM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology