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Effector differentiation by stem-like intraepithelial γδ T cells is required for host defense against infection

GSE309993 Mus musculus Expression profiling by high throughput sequencing 25 samples Submitted 2026/04/13 Platform GPL28457Platform GPL24247
Summary
Intraepithelial γδ T cells (γδIELs) are crucial for maintaining intestinal homeostasis, yet their functional regulation remains incompletely understood. Here, we identified two distinct γδIEL subsets: CD160+TCF1+BCL6+ stem-like and granzymeB+BLIMP1+ effector-like cells; the latter exhibited cytotoxic activity. Stem-like γδIELs differentiated into effector-like cells in response to microbiota and pathogen infection. IL-12, in cooperation with IL-15 and TCR signaling, activated a STAT4-BLIMP1 pathway to induce effector differentiation, and IL-12 signaling was required for their cytotoxic function. Tcf7 deletion significantly reduced stem-like but not effector-like γδIELs, while Bcl6 deficiency increased effector-like γδIELs selectively. In contrast, the absence of Prdm1 not only abolished the development of effector-like γδIELs but also impaired the clearance of enterogenous pathogens. Taken together, these findings define two functionally distinct γδIEL subsets with a hierarchical regulatory program linking microbial signals and cytokine pathways to their cytotoxic function in the gut.
Published in
Effector differentiation by stem-like intraepithelial γδ T cells is required for host defense against infection
Xie S, Xing Q, Zhang Q et al. · Immunity 2026 · PMID 41747734 · doi:10.1016/j.immuni.2026.01.006
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Direct links to NCBI, no account and no request form: the whole study as GSE309993_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 25 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1357327 and SRA study SRP641196. Searching any of these in the dataset finder brings you back here.

Study design
11 conditions, mostly in duplicate
SI_gd_Bcl6n ×3 SI_gd_Bcl6p ×3 LI_gd_Bcl6p ×2 CD160p_gd_Bcl6_WT ×2 CD160p_gd_Bcl6_KO ×2 total_gd_Prdm1_WT ×2 total_gd_Prdm1_KO ×2 CD160p_gd_Tcf7_WT ×2 +4 more

Supports a between-group comparison across 24 samples.

11 replicated groups read from 25 sample titles; they account for 24 of them. Check it against the sample list below before relying on it.

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