The endogenous danger signal uric Acid augments contact hypersensitivity responses in mice.
OBJECTIVE
The danger hypothesis proposes that the immune system responds not only to foreign antigens but also to damaged cells or tissues. Recently, uric acid crystals (monosodium urate, MSU) from necrotic cell lysates were identified as a danger signal for dendritic cells (DCs). Our aim was to determine whether MSU modulates immune responses in the skin.


METHODS
We analyzed the effect of MSU on trinitrochlorobenzene-induced contact hypersensitivity responses using BALB/c mice administered potassium oxonate, an uricase inhibitor, to prevent MSU degradation. Ear swelling response after elicitation and activation profiles of DCs and T cells in draining lymph nodes after sensitization were assessed.


RESULTS
Intradermal administration of MSU augmented the ear swelling response in potassium oxonate-administered mice and enhanced expression of CD86 and CD40 molecules on DCs in the lymph nodes. Activation of DCs was followed by an increase in CD69+ and CD44+ T cells in CD4+ and/or CD8+ subsets in the lymph nodes 4 days after trinitrochlorobenzene sensitization.


CONCLUSIONS
These observations demonstrate that MSU is an endogenous danger signal, which augments the contact hypersensitivity response in mice. MSU released from damaged skin may act as an endogenous adjuvant to augment immune response.
Liu
Lanlan
L
Department of Immunology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Inoue
Hiroko
H
Nakayama
Hirofumi
H
Kanno
Rieko
R
Kanno
Masamoto
M
D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002722:Chlorobenzenes / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D004431:Ear, External / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010094:Oxonic Acid / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014527:Uric Acid / Q000097:blood / Q000276:immunology*
D051940:B7-2 Antigen; D019013:CD40 Antigens; D002722:Chlorobenzenes; C036720:trichlorobenzene; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid