1. IL-23 drives differentiation of peripheral γδ17 T cells from adult bone marrow-derived precursors.
- Author
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Papotto PH, Gonçalves-Sousa N, Schmolka N, Iseppon A, Mensurado S, Stockinger B, Ribot JC, and Silva-Santos B
- Subjects
- Animals, Bone Marrow immunology, Bone Marrow pathology, Bone Marrow Transplantation, Cell Differentiation drug effects, Cell Lineage immunology, Cell Movement, Encephalomyelitis, Autoimmune, Experimental genetics, Encephalomyelitis, Autoimmune, Experimental pathology, Gene Expression Regulation, Hematopoiesis immunology, Interleukin-17 genetics, Interleukin-17 immunology, Interleukin-1beta genetics, Interleukin-1beta immunology, Interleukin-1beta pharmacology, Interleukin-23 genetics, Interleukin-23 pharmacology, Lymph Nodes pathology, Lymphocyte Activation drug effects, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, gamma-delta genetics, Receptors, Interleukin genetics, Receptors, Interleukin immunology, Signal Transduction, Th17 Cells pathology, Thymus Gland immunology, Thymus Gland pathology, Encephalomyelitis, Autoimmune, Experimental immunology, Interleukin-23 immunology, Lymph Nodes immunology, Receptors, Antigen, T-Cell, gamma-delta immunology, Th17 Cells immunology
- Abstract
Pro-inflammatory interleukin (IL)-17-producing γδ (γδ17) T cells are thought to develop exclusively in the thymus during fetal/perinatal life, as adult bone marrow precursors fail to generate γδ17 T cells under homeostatic conditions. Here, we employ a model of experimental autoimmune encephalomyelitis (EAE) in which hematopoiesis is reset by bone marrow transplantation and demonstrate unequivocally that Vγ4
+ γδ17 T cells can develop de novo in draining lymph nodes in response to innate stimuli. In vitro, γδ T cells from IL-17 fate-mapping reporter mice that had never activated the Il17 locus acquire IL-17 expression upon stimulation with IL-1β and IL-23. Furthermore, IL-23R (but not IL-1R1) deficiency severely compromises the induction of γδ17 T cells in EAE, demonstrating the key role of IL-23 in the process. Finally, we show, in a composite model involving transfers of both adult bone marrow and neonatal thymocytes, that induced γδ17 T cells make up a substantial fraction of the total IL-17-producing Vγ4+ T-cell pool upon inflammation, which attests the relevance of this novel pathway of peripheral γδ17 T-cell differentiation., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)- Published
- 2017
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