The transcription factor Aiolos restrains the activation of intestinal intraepithelial lymphocytes.

ABSTRACT: Intestinal intraepithelial lymphocytes (IELs) exhibit prompt innate-like responses to microenvironmental cues and require strict control of effector functions. Here we showed that Aiolos, an Ikaros zinc-finger family member encoded by Ikzf3, acted as a regulator of IEL activation. Ikzf3^-/- CD8αα⁺ IELs had elevated expression of NK receptors, cytotoxic enzymes, cytokines and chemokines. Single-cell RNA sequencing of Ikzf3^-/- and Ikzf3^+/+ IELs showed an amplified effector machinery in Ikzf3^-/- CD8αα⁺ IELs compared to Ikzf3^+/+ counterparts. Ikzf3^-/- CD8αα⁺ IELs had increased responsiveness to interleukin-15, which explained a substantial part, but not all, of the observed phenotypes. Aiolos bind

SUBMITTER: Yomogida K 

PROVIDER: S-EPMC11835375 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature