IL-23 drives differentiation of peripheral γδ17 T cells from adult bone marrow-derived precursors.

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.

• Authors: Pedro H Papotto, Natacha Gonçalves-Sousa, Nina Schmolka, Andrea Iseppon, Sofia Mensurado, Brigitta Stockinger, Julie C Ribot, Bruno Silva-Santos
• Journal: EMBO reports (EMBO Rep) Vol. 18 Issue 11 Pg. 1957-1967 (11 2017) ISSN: 1469-3178 [Electronic] England
• PMID: 28855306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Chemical References

• IL1B protein, mouse
• Interleukin-17
• Interleukin-1beta
• Interleukin-23
• Receptors, Antigen, T-Cell, gamma-delta
• Receptors, Interleukin
• interleukin-23 receptor, mouse

Topics

• Animals
• Bone Marrow (immunology, pathology)
• Bone Marrow Transplantation
• Cell Differentiation (drug effects)
• Cell Lineage (immunology)
• Cell Movement
• Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, pathology)
• Gene Expression Regulation
• Hematopoiesis (immunology)
• Interleukin-17 (genetics, immunology)
• Interleukin-1beta (genetics, immunology, pharmacology)
• Interleukin-23 (genetics, immunology, pharmacology)
• Lymph Nodes (immunology, pathology)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Receptors, Antigen, T-Cell, gamma-delta (genetics, immunology)
• Receptors, Interleukin (genetics, immunology)
• Signal Transduction
• Th17 Cells (immunology, pathology)
• Thymus Gland (immunology, pathology)