IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune-suppression

摘要

Both, mast cells (MC) and regulatory T cells (Treg) have gained attention as immunosuppressive cell populations. To investigate a possible interaction, we used the Th1- and Th17-dependent model of nephrotoxic serum nephritis (NTS), in which both MC and Treg have been shown to play a protective role.Transfer of wild-type (wt) Treg into wt recipients almost completely prevents development of NTS and leads to a profound increase of MC in the renal draining lymph nodes (LN). By contrast, transfer of wt Treg into animals deficient in MC, which are characterized by an exaggerated susceptibility to NTS, no longer exhibited protective effects. Blocking the pleiotropic cytokine IL-9, known to be involved in MC recruitment and proliferation, by means of a monoclonal antibody in mice receiving Treg abrogated protection from NTS. Moreover, transfer of IL-9 deficient Treg also failed to protect from NTS. In the absence of Treg-derived IL-9, MC fail to accumulate in the LN, despite the fact that IL-9 deficiency does not alter the general suppressive activity of Treg.In summary, we provide the first direct in vivo evidence that the nephroprotective, anti-inflammatory effects of Treg cells critically depend on IL-9-mediated attraction of MC into kidney-draining LN.