Introduction Dendritic cells (DCs) are a large family of leukocytes that unlike other antigen presenting cells (APCs), are thought to have no function other than regulate T and B cell responses. This function of DCs requires prior activation and is controlled by their state of maturation. Bone marrow-derived DCs migrate to the periphery as “immature” cells. Upon stimulation with microbial stimuli, they become “mature” and express high levels of major histocompatibility complex (MHC) class I and II, co-stimulatory and adhesion molecules. In recent study we demonstrated that exogenous Annexin-1 (Anx-A1) modulates T cell activation and differentiation (1). Given the key role of DC in influencing T cell response, in this study we sought to characterise the role of endogenous Anx-A1 in DC activation and as well as their capacity to influence T cell responses. Results Anx-A1+/+ and Anx-A1-/- DCs were obtained by culturing bone marrow cells from male mice (Balb/C or C57/BL6; aged 6-8 weeks) with GM-CSF derived from X63-GMCSF cell supernatants for 8 days. Analysis of the total number of cells collected after 8 days of differentiation showed a higher number of non-adherent cells from Anx-A1-/- mice compared to control littermate. Furthermore, analysis by FACS staining of markers of DC maturation in Anx-A1 deficient cells showed higher expression of MHC II, CD54, CD80 and CD86. Stimulation of DCs with lipopolysaccharide (LPS) displayed decreased TNF-α and increased IL-12 production in AnxA1-/-. Interestingly, analysis of NF-κB activation upon LPS stimulation showed lower DNA-binding activity in Anx-A1-/- DC compared to their control littermates. Finally, to study the effect on T cell activation, AnxA1+/+ and AnxA1-/- DCs were co-cultured in graded ratios with allogeneic CD4+ T cells in a mixed leukocyte reaction. Consistent with previous results co-culture of immature and mature DCs from the Anx-A1-/- mice with wild-type T cells in MLR showed increased proliferation and Th1 cytokine production. Conclusions Together these findings suggest that genetic deletion of Anx-A1 induces a previously undescribed phenotype in DCs i.e. increased yield of DC differentiation; increased Th1 skewing capability accompanied by and decrease in acute inflammatory cytokine production and increase in longer-term, immunomodulatory cytokine production.