| First Author | Ishikawa J | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1211620 | PubMed ID | 37662923 |
| Mgi Jnum | J:340323 | Mgi Id | MGI:7527202 |
| Doi | 10.3389/fimmu.2023.1211620 | Citation | Ishikawa J, et al. (2023) IL-21 is required for the maintenance and pathogenesis of murine Vgamma4(+) IL-17-producing gammadeltaT cells. Front Immunol 14:1211620 |
| abstractText | Murine IL-17-producing gammadeltaT (gammadeltaT17) cells are divided into two subsets: natural gammadeltaT17 (ngammadeltaT17) cells, whose development is restricted to the fetal thymus, and inducible gammadeltaT17 cells, which require antigen exposure for their IL-17 production and are presumed to develop from Rorc (+) Il17a (-) CCR9 (+) immature gammadeltaT17 cells in the adult thymus and whose T cell receptor (TCR) is biased toward Vgamma4. Although IL-23 is known to be involved in developing gammadeltaT17 cells, the roles of other cytokines, such as IL-21, which is involved in developing Th17 cells like IL-23, in the development, maintenance, and pathophysiology of gammadeltaT17 cells remain unknown. Here, we show that IL-21 is dispensable for the fetal thymic development of ngammadeltaT17 cells but is required for the peripheral maintenance of Vgamma4(+)ngammadeltaT17 cells. Upon stimulation with gammadeltaTCR, IL-1 plus IL-21 induces the proliferation of Vgamma4(+)ngammadeltaT17 cells via STAT3 as effectively as IL-1 plus IL-23. Using bone marrow chimeric mice, we demonstrated that immature gammadeltaT17 cells are produced de novo in the adult mice from donor adult bone marrow cells and that IL-21 is dispensable for their development. Instead, IL-21 is required to expand newly induced Vgamma4(+)gammadeltaT17 cells in the periphery upon immunization. Finally, using adoptive transfer experiments of gammadeltaT17 cells, we found that IL-21 receptors on gammadeltaT17 cells are involved in maintaining Vgamma4(+)gammadeltaT17 cells, subsequent infiltration of Th17 cells into the spinal cord, and exacerbation of experimental autoimmune encephalomyelitis. Collectively, IL-21 plays a vital role in the maintenance and pathogenesis of Vgamma4(+)gammadeltaT17 cells. |
