Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice

• Published in: The Journal of experimental medicine Vol. 216; no. 4; pp. 831 - 846
• Main Authors: Kimura, Shunsuke, Kobayashi, Nobuhide, Nakamura, Yutaka, Kanaya, Takashi, Takahashi, Daisuke, Fujiki, Ryoji, Mutoh, Mami, Obata, Yuuki, Iwanaga, Toshihiko, Nakagawa, Tomoo, Kato, Naoya, Sato, Shintaro, Kaisho, Tsuneyasu, Ohno, Hiroshi, Hase, Koji
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.04.2019
• Subjects: Animals; Antigens - immunology; Cell Differentiation - immunology; Epithelial Cells - metabolism; HEK293 Cells; Humans; Immunity, Mucosal - immunology; Immunoglobulin A - metabolism; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Peyer's Patches - cytology; Peyer's Patches - immunology; SOXE Transcription Factors - genetics; SOXE Transcription Factors - metabolism; Weaning
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20181604

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 to increase expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile -deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.