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Specific Expression of Apolipoprotein A-IV in the Follicle-Associated Epithelium of the Small Intestine

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Abstract

Background

Peyer’s patches (PPs), which are covered by specialized follicle-associated epithelium (FAE) including M cells, play a central role in immune induction in the gastrointestinal tract. This study is to investigate a new molecule to characterize PPs.

Methods

We generated a monoclonal antibody (mAb 10-15-3-3) that specifically reacts to the epithelium of PPs and isolated lymphoid follicles. Target antigen was analyzed by immunoprecipitation and mass spectrometry. Localization and expression of target antigen were evaluated by immunofluorescence, in situ hybridization and real-time PCR.

Results

Immunoprecipitation and mass spectrometry revealed that mAb 10-15-3-3 recognized apolipoprotein A-IV (ApoA-IV), a well-known lipid transporter; this finding was confirmed by the specific reactivity of mAb 10-15-3-3 to cells transfected with the murine ApoA-IV gene. Immunofluorescence using mAb 10-15-3-3 showed intestinal localization of ApoA-IV, in which strong expression of the ApoA-IV protein occurred throughout the entire intestinal epithelium during developing period before weaning but was restricted to the FAE in adult mice. In support of these findings, in situ hybridization showed strong expression of the ApoA-IV gene throughout the entire intestinal epithelium during developing period before weaning, but this expression was restricted to the FAE predominantly and the tips of villi to a lesser extent in adult mice. Deficiency of ApoA-IV had no effect on the organogenesis of PP in mice.

Conclusions

Our current results reveal ApoA-IV as a novel FAE-specific marker especially in the upper small intestine of adult mice.

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Acknowledgments

This work was supported by grants from the Grant-in-Aid for Research Activity Start-up of the Ministry of Education, Culture, Sports, Science and Technology of Japan; Young Researcher Overseas Visits Program for Vitalizing Brain Circulation of the Japan Society for the Promotion of Science (JSPS); the Japan Foundation for Pediatric Research; Houjinkai fellowship award of the Department of Pediatrics at Osaka City University Graduate School of Medicine; and the Association for Preventive Medicine of Japan.

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Daisuke Tokuhara, Tomonori Nochi, Akiko Matsumura, Mio Mejima, Yuko Takahashi, Shiho Kurokawa, Hiroshi Kiyono & Yoshikazu Yuki

  2. Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan

    Daisuke Tokuhara

Authors
  1. Daisuke Tokuhara
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  2. Tomonori Nochi
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  3. Akiko Matsumura
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  4. Mio Mejima
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  5. Yuko Takahashi
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  6. Shiho Kurokawa
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  7. Hiroshi Kiyono
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  8. Yoshikazu Yuki
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Corresponding author

Correspondence to Yoshikazu Yuki.

Electronic supplementary material

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10620_2014_3203_MOESM1_ESM.pptx

E.coli-derived recombinant murine ApoA-IV (0.5 mg in 0.4 ml) was intravenously injected to 8-week-old BL/6 wild-type mice or ApoA-IV gene knockout mice via tail vein. PBS (0.4 ml) was intravenously injected to ApoA-IV gene knockout mice via tail vein as a control. One hour later, peripheral blood was collected from each mouse, then their serum was applied for Western blot analysis using mAb (10-15-3-3). Western blot analysis using mAb (10-15-3-3) disclosed that mAb-recognized 45 kDa of protein in rApoA-IV-injected ApoA-IV gene knockout mice and wild-type mice but not in PBS-injected ApoA-IV gene knockout mice (PPTX 122 kb)

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Tokuhara, D., Nochi, T., Matsumura, A. et al. Specific Expression of Apolipoprotein A-IV in the Follicle-Associated Epithelium of the Small Intestine. Dig Dis Sci 59, 2682–2692 (2014). https://doi.org/10.1007/s10620-014-3203-6

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  • DOI: https://doi.org/10.1007/s10620-014-3203-6

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