TY - JOUR
T1 - Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice
AU - Kimura, Shunsuke
AU - Kobayashi, Nobuhide
AU - Nakamura, Yutaka
AU - Kanaya, Takashi
AU - Takahashi, Daisuke
AU - Fujiki, Ryoji
AU - Mutoh, Mami
AU - Obata, Yuuki
AU - Iwanaga, Toshihiko
AU - Nakagawa, Tomoo
AU - Kato, Naoya
AU - Sato, Shintaro
AU - Kaisho, Tsuneyasu
AU - Ohno, Hiroshi
AU - Hase, Koji
N1 - Publisher Copyright:
© 2019 Kimura et al.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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 number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-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.
AB - 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 number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-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.
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U2 - 10.1084/jem.20181604
DO - 10.1084/jem.20181604
M3 - Article
C2 - 30877171
AN - SCOPUS:85064206035
SN - 0022-1007
VL - 216
SP - 831
EP - 846
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -