Roles for TGF-beta and programmed cell death 1 ligand 1 in regulatory T cell expansion and diabetes suppression by zymosan in nonobese diabetic mice.
Zymosan is a complex fungal component shown to be capable of both promoting and suppressing the development of autoimmune disorders in mice. In this study, we show that a single injection of zymosan just prior to diabetes onset can significantly delay the progression of disease in NOD mice. Zymosan treatment of NOD mice induced the production of biologically active TGF-beta from cells infiltrating the pancreas and was associated with expansion of programmed cell death 1 ligand 1(+)TGF-beta(+) macrophages and Foxp3(+) regulatory T cells in vivo. Neutralization of either TGF-beta or programmed cell death 1 ligand 1 abrogated the protective effects of zymosan. Zymosan acted through TLR2 as well as ERK and p38 MAPK to induce macrophage secretion of TGF-beta and promotion of Foxp3(+) regulatory T cells in vitro and in vivo.
Burton
Oliver T
OT
Department of Pathology, University of Cambridge, Cambridge, UK. olivertburton@gmail.com
Zaccone
Paola
P
Phillips
Jenny M
JM
De La Peña
Hugo
H
Fehérvári
Zoltán
Z
Azuma
Miyuki
M
Gibbs
Sarah
S
Stockinger
Brigitta
B
Cooke
Anne
A
D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D008907:Mink; D010455:Peptides / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015054:Zymosan / Q000008:administration & dosage* / Q000627:therapeutic use
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D016212:Transforming Growth Factor beta; D015054:Zymosan