上海士鋒生物關(guān)于M細(xì)胞的介紹

最近更新時間：2013-6-7

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資料圖片：M細(xì)胞包圍住大腸桿菌

M細(xì)胞（Membranous / microfold cell）扁平細(xì)胞，是散布于腸道黏膜上皮細(xì)胞間的一種特化的抗原運轉(zhuǎn)細(xì)胞。它不表達(dá)MHCⅡ類分子，胞質(zhì)內(nèi)溶毛體很少，在腸黏膜表面有短小不規(guī)則毛刷樣微絨毛。它具有高度的非特異性脂酶活性。病原菌等外來抗原性物質(zhì)可通過對M細(xì)胞表面的毛刷狀微絨毛的吸附，或經(jīng)M細(xì)胞表面蛋白酶作用后被攝取。

粘膜免疫系統(tǒng)在保護(hù)粘膜表面不受病原體侵害、在促進(jìn)與共生微生物群落共生中都起主要作用。要激發(fā)粘膜免疫反應(yīng)，粘膜表面上的抗原必須首先穿過不可透過的上皮障礙，進(jìn)入“派伊爾小結(jié)”這樣的淋巴結(jié)構(gòu)。這一功能（被稱為“轉(zhuǎn)胞吞作用”）被認(rèn)為主要由M細(xì)胞調(diào)控，它們是“派伊爾小結(jié)”中專門的上皮細(xì)胞。對由M-細(xì)胞調(diào)控的抗原“轉(zhuǎn)胞吞作用”的機(jī)制所做的一項研究表明，在小腸M細(xì)胞頂面表達(dá)的糖蛋白-2是表達(dá)FimH抗原的細(xì)菌的轉(zhuǎn)胞吞受體。由于M-細(xì)胞被認(rèn)為是各種口服免疫藥物的一個很有希望的目標(biāo)，所以這項工作表明，依賴于糖蛋白-2的“轉(zhuǎn)胞吞作用”是一個可能的免疫目標(biāo)。

Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response

Koji Hase1,10, Kazuya Kawano1,10, Tomonori Nochi2, Gemilson Soares Pontes2, Shinji Fukuda1,3, Masashi Ebisawa1,3, Kazunori Kadokura1,3, Toru Tobe4, Yumiko Fujimura1, Sayaka Kawano1, Atsuko Yabashi5, Satoshi Waguri5, Gaku Nakato1,3, Shunsuke Kimura1, Takaya Murakami1, Mitsutoshi Iimura6, Kimiyo Hamura6, Shin-Ichi Fukuoka7, Anson W. Lowe8, Kikuji Itoh9, Hiroshi Kiyono2 & Hiroshi Ohno1,3

1 Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, Kanagawa 230-0045, Japan
2 Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
3 Supramolecular Biology, International Graduate School of Bionanoscience, Yokohama City University, Kanagawa 230-0045, Japan
4 Graduate School of Medicine, Osaka University, 565-0871 Suita, Osaka, Japan
5 Department of Anatomy and Histology, Fukushima Medical University, School of Medicine, Fukushima 960-1295, Japan
6 Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo 162-8666, Japan
7 Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, Kanagawa, 229-8558, Japan
8 Department of Medicine and the Digestive Disease Center, Stanford University, Stanford, California 94305, USA
9 Veterinary Public Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
10 These authors contributed equally to this work.
Correspondence to: Hiroshi Ohno1,3 Correspondence and requests for materials should be addressed to H.O.

The mucosal immune system forms the largest part of the entire immune system, containing about three-quarters of all lymphocytes and producing grams of secretory IgA daily to protect the mucosal surface from pathogens1, 2, 3. To evoke the mucosal immune response, antigens on the mucosal surface must be transported across the epithelial barrier into organized lymphoid structures such as Peyer's patches4. This function, called antigen transcytosis, is mediated by specialized epithelial M cells5, 6. The molecular mechanisms promoting this antigen uptake, however, are largely unknown. Here we report that glycoprotein 2 （GP2）, specifically expressed on the apical plasma membrane of M cells among enterocytes, serves as a transcytotic receptor for mucosal antigens. Recombinant GP2 protein selectively bound a subset of commensal and pathogenic enterobacteria, including Escherichia coli and Salmonella enterica serovar Typhimurium （S. Typhimurium）, by recognizing FimH, a component of type I pili on the bacterial outer membrane. Consistently, these bacteria were colocalized with endogenous GP2 on the apical plasma membrane as well as in cytoplasmic vesicles in M cells. Moreover, deficiency of bacterial FimH or host GP2 led to defects in transcytosis of type-I-piliated bacteria through M cells, resulting in an attenuation of antigen-specific immune responses in Peyer's patches. GP2 is therefore a previously unrecognized transcytotic receptor on M cells for type-I-piliated bacteria and is a prerequisite for the mucosal immune response to these bacteria. Given that M cells are considered a promising target for oral vaccination against various infectious diseases7, 8, the GP2-dependent transcytotic pathway could provide a new target for the development of M-cell-targeted mucosal vaccines.

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