ArticleImmunological investigations2025
Renal Tubular Epithelial Cell-Derived IL-7 Drives Expansion and Protective Effects of Double-Negative T Cells in Acute Kidney Injury.
Article in Immunological investigations, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPrevious studies have demonstrated that double-negative (DN) αβ T cells play an important role in immune responses during ischemic acute kidney injury (AKI). Here, we investigate the role of γ-chain cytokines in driving DN T cell proliferation in steady state and AKI, focusing on IL-2, IL-7, and IL-15.
methodsWe assessed DN T cell proliferation in vitro in response to IL-2, IL-7, and IL-15, with co-culture experiments using renal tubular epithelial cells (RTECs) and IL-7 blockade. In vivo, wild-type and IL-7r knockout mice were studied to evaluate the impact of IL-7 on DN T cell expansion and kidney function during AKI. Human RTECs confirmed the relevance of these findings.
resultsAll three cytokines promoted DN T cell proliferation in vitro, with IL-7 inducing the most robust expansion. Co-culture experiments showed RTECs as a key IL-7 source, and blockade reduced DN T cell expansion. In vivo, IL-7 complexes administered to wild-type mice increased DN T cells and selectively expanded the PD-1+ subset. IL-7 deficiency worsened renal outcomes during AKI. Human RTECs activated peripheral human DN T cells in vitro.
conclusionThese results establish IL-7 as pivotal for DN T cell expansion and highlight RTECs' role in DN T cell homeostasis.
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