The transcription factor T-bet is best known for its role in T helper 1 (TH1)-cell differentiation, but now new data indicate that T-bet expression by dendritic cells (DCs) is also required for pro-inflammatory cytokine production and T-cell priming.

Photograph by Daniel Jones

Because T-bet is highly expressed in tissues affected by rheumatoid arthritis in humans, Glimcher and colleagues set out to evaluate the role of T-bet in a mouse model of arthritis, collagen-antibody-induced arthritis (CAIA). In this model, disease is induced by administration of monoclonal antibodies specific for type II collagen together with lipopolysaccharide and is characterized by an early innate phase followed by a later adaptive phase. Compared with wild-type mice, the onset of CAIA in T-bet-deficient mice was delayed and was less severe in both the initial and the late phases. Mice that are deficient in RAG2 (recombination-activating gene 2), which completely lack B and T cells, developed early joint inflammation, but the later phase was attenuated. And mice that are deficient in both T-bet and RAG2 were resistant to the induction of arthritis.

To further assess the cellular components of the innate phase, the authors carried out adoptive-transfer experiments. Transfer of wild-type DCs to T-bet-deficient mice on day 1 of CAIA induction restored inflammatory arthritis, and wild-type DCs restored the early phase response when transferred to mice that are deficient in both T-bet and RAG2. Consistent with this role for DCs in the early inflammatory phase, the authors showed that T-bet-deficient DCs produced less of the pro-inflammatory mediators interleukin-1α and CC-chemokine ligand 3 (CCL3) and more CCL17, a ligand for the TH2-cell-specific chemokine receptor CCR4, than wild-type DCs. Moreover, the ability of DCs to prime naive T cells in vivo was impaired in the absence of T-bet.

In light of these results, T-bet could be a target to control inflammation at multiple points in both innate and adaptive immune responses.