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 - Funding Information:
This study was supported by JSPS KAKENHI grants JP16J09413 (N. Kobayashi), JP16H06598 (M. Mutoh), JP25460261 and JP16K08457 (S. Kimura), and JP25293114 and JP17H04089 (K. Hase). The authors declare no competing financial interests.
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
VL - 216
SP - 831
EP - 846
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 4
ER -