Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells

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Abstract

The transcription factor T-bet (Tbx21) plays a major role in adaptive immunity and is required for optimal IFN-γ production by DCs. Here we demonstrate an essential function for T-bet in DCs in controlling inflammatory arthritis. We show that collagen antibody-induced arthritis (CAIA), a model of human RA, is a bipartite disease characterized by an early innate immune system component intact in RAG2 -/- mice and a later adaptive immune system phase. Mice lacking T-bet had markedly reduced joint inflammation at both early and late time points and RAG2 -/-T-bet -/- double-deficient mice were essentially resistant to disease. Remarkably, adoptive transfer of T-bet-expressing DCs reconstituted inflammation in a T-bet deficient and T-bet/RAG2-deficient milieu. T-bet regulates the production of proinflammatory cytokine IL-1α and chemokines macrophage inflammatory protein-1α (MIP-1α) and thymus- and activation-related chemokine (TARC) by DCs. Further, T-bet expression in DCs is required for T helper cell activation. We conclude that T-bet plays a vital function in DCs that links innate and adaptive immunity to regulate inflammatory responses. T-bet provides an attractive new target for the development of novel therapeutics for inflammatory arthritis.

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Wang, J., Fathman, J. W., Lugo-Villarino, G., Scimone, L., Von Andrian, U., Dorfman, D. M., & Glimcher, L. H. (2006). Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. Journal of Clinical Investigation, 116(2), 414–421. https://doi.org/10.1172/JCI26631

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