Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells.
The transcription factor T-bet ( Tbx21) plays a major role in adaptive immunity and is required for optimal IFN-gamma 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 RAG2T-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-1alpha and chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) 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.[1]References
- Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. Wang, J., Fathman, J.W., Lugo-Villarino, G., Scimone, L., von Andrian, U., Dorfman, D.M., Glimcher, L.H. J. Clin. Invest. (2006) [Pubmed]
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