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.
Highlights
Interleukin (IL)-17A (IL-17 ) is a major promoter of antimicrobial peptide production and neutrophil mobilization, which likely accounts for its conservation across evolution of the vertebrate immune system [1]
We show, in a composite model involving transfers of both adult bone marrow and neonatal thymocytes, that induced cd17 T cells make up a substantial fraction of the total IL-17-producing Vc4+ T-cell pool upon inflammation, which attests the relevance of this novel pathway of peripheral cd17 T-cell differentiation
While CD4+ ab T cells are certainly the better known producers of IL-17, defining the “T helper 17” (TH17) cell lineage [3,4,5], they are often preceded and outnumbered at earlier stages of immune responses by cd T cells [6]. These can mount very rapid IL-17-based responses that drive neutrophil recruitment and control microbial load, as documented in multiple infection settings: Listeria monocytogenes in the liver [7]; Escherichia coli in the peritoneal cavity [8]; Bordetella pertussis in the lung [9]; Mycobacterium bovis-BCG in the skin [10]; and Candida albicans and Pseudomonas aeruginosa in the eye [11], among others
Summary
Interleukin (IL)-17A (IL-17 ) is a major promoter of antimicrobial peptide production and neutrophil mobilization, which likely accounts for its conservation across evolution of the vertebrate immune system [1]. While CD4+ ab T cells are certainly the better known producers of IL-17, defining the “T helper 17” (TH17) cell lineage [3,4,5], they are often preceded and outnumbered at earlier stages of immune responses by cd T cells [6] These can mount very rapid IL-17-based responses that drive neutrophil recruitment and control microbial load, as documented in multiple infection settings: Listeria monocytogenes in the liver [7]; Escherichia coli in the peritoneal cavity [8]; Bordetella pertussis in the lung [9]; Mycobacterium bovis-BCG in the skin [10]; and Candida albicans and Pseudomonas aeruginosa in the eye [11], among others (reviewed in Ref. 12). This has been demonstrated in mouse models of diseases such as arthritis [13], colitis [14], uveitis [15], type 1 diabetes (T1D) [16], psoriasis [17,18,19], and multiple sclerosis [20,21,22]
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