Nature Immunology, Published online: 14 July 2025; doi:10.1038/s41590-025-02207-6

Bromley and colleagues show that IL-4 decreases the responsiveness of CD8+ T cells to TGFβ, resulting in impaired formation of CD8+ TRM cells.



Summary

Bromley et al. in Nature Immunology (July 2025) report a novel mechanism regulating CD8+ tissue-resident memory (TRM) cell formation. Their research demonstrates that the cytokine interleukin-4 (IL-4) weakens CD8+ T cell sensitivity to transforming growth factor-beta (TGFβ). This diminished responsiveness impairs the crucial TGFβ signaling pathway, ultimately hindering the development of CD8+ TRM cells, which are vital for long-term immunity within tissues. The findings shed light on the complex interplay of cytokines in regulating immune cell differentiation and tissue residence.

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