Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation.
Piconese, Silvia ; Gri, Giorgia ; Tripodo, Claudio ; et al. ; - ASI Sponsor
Sep - 2009
ISSN : 1528-0020 ;
journal : Blood

Issue : 13
type: Article Journal

The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell-derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17-producing T cells (Th17). In vivo analysis of lymph nodes hosting T-cell priming in experimental autoimmune encephalomyelitis revealed activated MCs, Tregs, and Th17 cells displaying tight spatial interactions, further supporting the occurrence of an MC-mediated inhibition of Treg suppression in the establishment of Th17-mediated inflammatory responses.

keywords : Animals,Cell Differentiation,Cell Differentiation: immunology,Cell Proliferation,Cells,Congenic,Cultured,Helper-Inducer,Helper-Inducer: immunology,Helper-Inducer: metabolism,Helper-Inducer: physiology,Immune Tolerance,Immune Tolerance: immunology,Inbred C57BL,Interleukin-17,Interleukin-17: metabolism,Interleukin-6,Interleukin-6: metabolism,Interleukin-6: physiology,Lymphocyte Activation,Lymphocyte Activation: immunology,Mast Cells,Mast Cells: immunology,Mast Cells: metabolism,Mast Cells: physiology,Membrane Glycoproteins,Membrane Glycoproteins: metabolism,Membrane Glycoproteins: physiology,Mice,OX40,OX40: metabolism,OX40: physiology,Receptors,Regulatory,Regulatory: immunology,Regulatory: metabolism,Regulatory: physiology,Signal Transduction,Signal Transduction: immunology,T-Lymphocytes,Transgenic,Tumor Necrosis Factors,Tumor Necrosis Factors: metabolism,Tumor Necrosis Factors: physiology