IL-23 drives differentiation of peripheral [gamma][delta]17 T cells from adult bone marrow-derived precursors

• Published in: EMBO reports 2017-11, Vol.18 (11), p.1957
• Main Authors: Papotto, Pedro H, Goncalves-Sousa, Natacha, Schmolka, Nina, Iseppon, Andrea, Mensurado, Sofia, Stockinger, Brigitta, Ribot, Julie C, Silva-Santos, Bruno
• Format: Article
• Language: English
• Subjects: Antigens; Bone marrow; Bone marrow transplantation; Cell differentiation; Cell fate; Differentiation (biology); Drainage; Experimental allergic encephalomyelitis; Fate maps; Fetuses; Hematopoiesis; Hemopoiesis; Inflammation; Interleukin 1; Interleukin 1 receptors; Interleukin 17; Interleukin 23; Interleukins; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Neonates; Osteoprogenitor cells; T cell receptors; Thymocytes; Thymus; Transplantation
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201744200

Pro-inflammatory interleukin (IL)-17-producing [gamma][delta] ([gamma][delta]17) T cells are thought to develop exclusively in the thymus during fetal/perinatal life, as adult bone marrow precursors fail to generate [gamma][delta]17 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 V[gamma]4+ [gamma][delta]17 T cells can develop de novo in draining lymph nodes in response to innate stimuli. In vitro, [gamma][delta] T cells from IL-17 fate-mapping reporter mice that had never activated the Il17 locus acquire IL-17 expression upon stimulation with IL-1[beta] and IL-23. Furthermore, IL-23R (but not IL-1R1) deficiency severely compromises the induction of [gamma][delta]17 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 [gamma][delta]17 T cells make up a substantial fraction of the total IL-17-producing V[gamma]4+ T-cell pool upon inflammation, which attests the relevance of this novel pathway of peripheral [gamma][delta]17 T-cell differentiation. Synopsis [gamma][delta]17 T cells are thought to develop exclusively in the fetal/perinatal thymus. This study shows that differentiation of [gamma][delta]17 T cells is also driven by IL-23 in inflamed lymph nodes in a mouse model of MS, independent of specific antigens. V[gamma]4+ [gamma][delta]17 T cells differentiate de novo in draining lymph nodes in a mouse model of experimental autoimmune encephalomyelitis (EAE). IL-23/IL-23R signals drive the peripheral differentiation of [gamma][delta]17 T cells. Peripherally induced [gamma][delta]17 T cells comprise a large fraction of [gamma][delta]17 T cells in EAE.