| First Author | Wang J | Year | 2006 |
| Journal | J Clin Invest | Volume | 116 |
| Issue | 2 | Pages | 414-21 |
| PubMed ID | 16410834 | Mgi Jnum | J:105447 |
| Mgi Id | MGI:3615086 | Doi | 10.1172/JCI26631 |
| Citation | Wang J, et al. (2006) Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. J Clin Invest 116(2):414-21 |
| abstractText | 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. |
