GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309993/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309993GEOGSEfalseEffector differentiation by stem-like intraepithelial γδ T cells is required for host defense against infectionIntraepithelial 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.2026/04/13GSE309993GSM9286206GSM9286207GSM9286208GSM9286209GSM9286198GSM9286210GSM9286199GSM9286211GSM9286194GSM9286195GSM9286196GSM9286197GSM9286190GSM9286191GSM9286192GSM9286193GSM9286202GSM9286203GSM9286204GSM9286205GSM9286187GSM9286188GSM9286189GSM9286200GSM92862012845724247309993Mus musculus[41747734]