马萨诸塞州总医院Shannon K. Bromley团队的最新研究揭示了IL-4损害皮肤驻留记忆CD8⁺ T细胞的形成。相关论文发表在2025年7月14日出版的《自然—免疫学》杂志上。

在这里，该团队发现IL-4抑制CD8⁺ T细胞获得上皮TRM细胞表型。IL-4通过激活CD8+ T细胞，抑制TGFβ诱导的CD103和CD49a的表达，提高Eomes的表达。这种表型变化与TGFβRII的持续下调、pSmad2/3的表达减少和抑制性Smad7的表达增加有关。在激活过程中暴露于IL-4的初始CD8⁺ T细胞表现出CD103⁺CD8⁺ TRM细胞形成受损。此外，特应性皮炎病变内产生的IL-4降低了浸润性CD8⁺ T细胞中CD103的表达，减少了CD8⁺ TRM细胞的形成，从而降低了对皮肤单纯疱疹病毒感染的保护作用。总之，这些发现表明，IL-4降低了CD8⁺ T细胞对TGFβ的反应性，导致CD8⁺ TRM细胞的形成受损，CD8⁺ TRM细胞介导的局部感染保护受损。

据介绍，局部细胞因子，包括TGFβ，驱动CD8⁺组织驻留记忆T （TRM）细胞在组织内的分化和长期持久性。然而，阻止CD8⁺ TRM细胞形成的信号尚未明确。

附：英文原文

Title: IL-4 impairs the formation of skin-resident memory CD8+ T cells

Author: Mora-Buch, Rut, Lake, Maisie E., Sama, Andrea, Chasse, Alexandra Y., Akbaba, Hasan, Mani, Vinidhra, Bromley, Shannon K.

Issue&Volume: 2025-07-14

Abstract: Local cytokines, including TGFβ, drive CD8+ tissue-resident memory T (TRM) cell differentiation and long-term persistence within tissues. However, the signals that prevent CD8+ TRM cell formation are not well defined. Here we found that IL-4 suppressed CD8+ T cell acquisition of an epithelial TRM cell phenotype. IL-4 inhibited the expression of TGFβ-induced CD103 and CD49a and increased the expression of Eomes by activated CD8+ T cells in vitro and in vivo. This change in phenotype was correlated with prolonged downregulation of TGFβRII, decreased expression of pSmad2/3 and increased expression of inhibitory Smad7. Naive CD8+ T cells exposed to IL-4 during activation exhibited impaired cutaneous CD103+CD8+ TRM cell formation. Additionally, IL-4 produced within atopic dermatitis lesions decreased the expression of CD103 in infiltrating CD8+ T cells and reduced CD8+ TRM cell formation, resulting in reduced protection from cutaneous herpes simplex virus infection. Together, these findings reveal that IL-4 decreases the responsiveness of CD8+ T cells to TGFβ, resulting in impaired formation of CD8+ TRM cells and impaired CD8+ TRM cell-mediated protection from local infection.

DOI: 10.1038/s41590-025-02207-6

Source: https://www.nature.com/articles/s41590-025-02207-6