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. METHOD: 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. CONCLUSION: 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.
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. METHOD: 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. CONCLUSION: 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.
Authors: Ana Isabel Sebastião; Isabel Ferreira; Gonçalo Brites; Ana Silva; Bruno Miguel Neves; Maria Teresa Cruz Journal: Pharmaceutics Date: 2020-09-11 Impact factor: 6.321