Intestinal Villous M Cells: An Antigen Entry Site in the Mucosal Epithelium

M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be the principal sites for the sampling of gut luminal antigens. Thus, PP have long been considered the gatekeepers of the mucosal immune system. Here, we report a distinct gateway for the uptake of gut b...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 101; no. 16; pp. 6110 - 6115
Main Authors Jang, Myoung Ho, Kweon, Mi-Na, Iwatani, Koichi, Yamamoto, Masafumi, Terahara, Kazutaka, Sasakawa, Chihiro, Suzuki, Toshihiko, Nochi, Tomonori, Yokota, Yoshifumi, Rennert, Paul D., Hiroi, Takachika, Tamagawa, Hiroshi, Iijima, Hideki, Kunisawa, Jun, Yuki, Yoshikazu, Kiyono, Hiroshi, Curtiss, Roy
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 20.04.2004
National Acad Sciences
Subjects
Animals
Antigens
Antigens - immunology
B lymphocytes
Bacteria
Bacterial Adhesion
Biological Sciences
Cellular immunity
E coli
Epithelial cells
Epithelium
Gastrointestinal diseases
Immune system
Immunology
Intestinal Mucosa - cytology
Intestinal Mucosa - immunology
Intestinal Mucosa - microbiology
Intestinal Mucosa - ultrastructure
Intestines
Lymphocytes
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron
Peyer's Patches - immunology
Salmonella
Salmonella typhimurium - physiology
Small intestine
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Summary:M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be the principal sites for the sampling of gut luminal antigens. Thus, PP have long been considered the gatekeepers of the mucosal immune system. Here, we report a distinct gateway for the uptake of gut bacteria: clusters of non-follicle-associated epithelium-associated Ulex europaeus agglutinin ( UEA)-1+ cells, which we have designated intestinal villous M cells. Interestingly, villous M cells are developed in various PP [or gut-associated lymphoid tissue (GALT)]. null mice, such as in utero lymphotoxin β receptor (LTβR)-Ig-treated, lymphotoxin α ( LTα)-/-, tumor necrosis factor/ LTα -/-, and inhibition of differentiation 2( Id2)-/- mice. Intestinal villous M cells have been observed to take up GFP-expressing Salmonella, Yersinia, and Escherichia coli-expressing invasin, as well as gut bacterial antigen for subsequent induction of antigen-specific immune responses. Thus, the identified villous M cells could be an alternative and PP-independent gateway for the induction of antigen-specific immune responses by means of the mucosal compartment.
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To whom correspondence should be addressed at the d address. E-mail: kiyono@ims.u-tokyo.ac.jp.
M.H.J. and M.-N.K. contributed equally to this work.
Abbreviations: PP, Peyer's patches; FAE, follicle-associated epithelium; LT, lymphotoxin; TNF, tumor necrosis factor; WGA, wheat germ agglutinin; UEA, Ulex europaeus agglutinin; TRITC, tetramethylrhodamine B isothiocyanate; IEC, intestinal epithelial cell; ILF, isolated lymphoid follicle; GALT, gut-associated lymphoid tissue; Id2, inhibition of differentiation 2.
Communicated by Roy Curtiss, Washington University, St. Louis, MO, February 11, 2004
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0400969101