| First Author | Wang S | Year | 2024 |
| Journal | Front Immunol | Volume | 15 |
| Pages | 1340467 | PubMed ID | 38348035 |
| Mgi Jnum | J:350740 | Mgi Id | MGI:7594555 |
| Doi | 10.3389/fimmu.2024.1340467 | Citation | Wang S, et al. (2024) Roles of tumor necrosis factor-like ligand 1A in gammadeltaT-cell activation and psoriasis pathogenesis. Front Immunol 15:1340467 |
| abstractText | BACKGROUND: Interleukin (IL)-17-producing gammadeltaT (gammadeltaT17) cells mediate inflammatory responses in barrier tissues. Dysregulated gammadeltaT17 cell activation can lead to the overproduction of IL-17 and IL-22 and the development of inflammatory diseases, including psoriasis. IL-23 and IL-1beta are known to synergistically activate gammadeltaT17 cells, but the regulatory mechanisms of gammadeltaT17 cells have not been fully elucidated. This study aimed to reveal the contribution of the inflammatory cytokine tumor necrosis factor-like ligand 1A (TL1A) to gammadeltaT17 cell activation and psoriasis development. METHODS: Anti-TL1A antibody was injected into an imiquimod (IMQ)-induced murine psoriasis model. TL1A receptor expression was analyzed in splenic and dermal gammadeltaT cells. gammadeltaT cells were tested for cytokine production in vitro and in vivo under stimulation with IL-23, IL-1beta, and TL1A. TL1A was applied to a psoriasis model induced by intradermal IL-23 injection. Mice deficient in gammadeltaT cells were intradermally injected with IL-23 plus TL1A to verify the contribution of TL1A-dependent gammadeltaT-cell activation to psoriasis development. RESULTS: Neutralization of TL1A attenuated gammadeltaT17 cell activation in IMQ-treated skin. TL1A induced cytokine production by splenic gammadeltaT17 cells in synergy with IL-23. Dermal gammadeltaT17 cells constitutively expressed a TL1A receptor at high levels and vigorously produced IL-22 upon intradermal IL-23 and TL1A injection but not IL-23 alone. TL1A exacerbated the dermal symptoms induced by IL-23 injection in wild-type but not in gammadeltaT cell-deficient mice. CONCLUSION: These findings suggest a novel regulatory mechanism of gammadeltaT cells through TL1A and its involvement in psoriasis pathogenesis as a possible therapeutic target. |
