Over the past years, it has become clear that Tumor Necrosis Factor (TNF) is a key player in the pathogenesis of spondyloarthritis, a disease leading to joint inflamemation of axial skeleton and peripheral joints, but the mechanisms by which this occurs are only partially known. Particularly, the cellular targets sufficient to mediate the articular and extra-articular manifestations (gut and skin inflammation) of spondyloarthritis remained to be defined, as well as the cellular constituents capable of modulating this TNF driven inflammation. Recently, we reported a peculiar role for mesenchymal cells in a mouse model of spondyloarthritis, characterized by enhanced TNF mRNA stability, resulting in Crohn's like ileitis as well as peripheral arthritis. Hence, TNF-R1 expression on mesenchymal cells was sufficient to mediate combined gut and joint pathologies in this model of murine spondyloarthritis. However, it remained unclear whether regulatory T cell subsets could modulate this inflammation. More recently, we uncovered that a particular regulatory T cell lineage, invariant NKT (iNKT) cells, are natural regulators of TNF driven inflammation by modulating maturation and differentiation of antigen presenting cells in a pathway that is strictly dependent upon TNF. Altogether, these observations provide new insights in the regulatory as well as the effector mechanisms of spondyloarthritis.