biostudies-literatureKimura SJSPS831-846https://www.ebi.ac.uk/biostudies/studies/S-EPMC6446867biostudies-literatureUnknown216(4)Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. The expression of Sox8 requires activation of RANKL-RelB signaling. Chromatin immunoprecipitation and luciferase assays revealed that Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the The Journal of experimental medicineSox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice.PMC6446867JP16H06598JP16J09413JP25460261JP17H04089JP25293114JP16K08457Obata YTakahashi DKimura SKobayashi NMutoh MSato SNakamura YKato NFujiki RNakagawa TKanaya TIwanaga TKaisho TOhno HHase KfalseSox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice.Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. The expression of Sox8 requires activation of RANKL-RelB signaling. Chromatin immunoprecipitation and luciferase assays revealed that Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the 2019-01-01T00:00:00Z2019 Apr2025-05-18T10:47:07.099Z2025-05-18T10:47:07.099ZS-EPMC64468673087717110.1084/jem.20181604