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Tipo do documento: Artigo
Título: Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis
Autor: Abdollahi-Roodsaz, Shahla
Joosten, Leo A. B.
Koenders, Marije I.
Devesa, Isabel
Roelofs, Mieke F.
Radstake, Timothy R. D. J.
Heuvelmans-Jacobs, Marleen
Akira, Shizuo
Nicklin, Martin J. H.
Dias, Fátima Ribeiro
Berg, Wim B. van den
Abstract: TLRs may contribute to the progression of rheumatoid arthritis through recognition of microbial or host- derived ligands found in arthritic joints. Here, we show that TLR2 and TLR4, but not TLR9, are involved in the pathogenesis of autoimmune arthritis and play distinct roles in the regulation of T cells and cytokines. We investigated the involvement of TLR2, TLR4, and TLR9 in the progression of arthritis using IL-1 receptor antagonist–knockout (IL1rn –/– ) mice, which spontaneously develop an autoimmune T cell–mediated arthritis. Spontaneous onset of arthritis was dependent on TLR activation by microbial flora, as germ-free mice did not develop arthritis. Clinical and histopathological evaluation of IL1rn –/– Tlr2 –/– mice revealed more severe arthritis, characterized by reduced suppressive function of Tregs and substantially increased IFN-γ produc- tion by T cells. IL1rn –/– Tlr4 –/– mice were, in contrast, protected against severe arthritis and had markedly lower numbers of Th17 cells and a reduced capacity to produce IL-17. A lack of Tlr9 did not affect the progression of arthritis. While any therapeutic intervention targeting TLR2 still seems complicated, the strict position of TLR4 upstream of a number of pathogenic cytokines including IL-17 provides an interesting potential thera- peutic target for rheumatoid arthritis.
País: Estados unidos
Unidade acadêmica: Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
Citação: ABDOLLAHI-ROODSAZ, Shahla; JOOSTEN, Leo A. B.; KOENDERS, Marije I.; DEVESA, Isabel; ROELOFS, Mieke F.; RADSTAKE, Timothy R. D. J.; HEUVELMANS-JACOBS, Marleen; AKIRA, Shizuo; NICKLIN, Martin J. H.; RIBEIRO-DIAS, Fátima; BERG, Wim B. van den. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. The Journal of Clinical Investigation, Michigan, v. 118, n. 1, p. 205-216, Jan. 2008.
Tipo de acesso: Acesso Aberto
Identificador do documento: 10.1172/JCI32639
Identificador do documento: 10.1172/JCI32639
Data de publicação: Jan-2008
Aparece nas coleções:IPTSP - Artigos publicados em periódicos

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