Cyclophilin A is a new M cell marker of bovine intestinal epithelium
Tetsuya Hondo1, Shunsuke Someya1, Yuya Nagasawa1
1Cellar Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori Amamiyamachi, Aoba-ku, 981-8555, Sendai, Japan.
Abstract:
Microfold (M) cells in the follicle-associated epithelium (FAE) of Peyer's patches contribute to the mucosal immune response by the transcytosis of microorganisms. The mechanism by which M cells take up microorganisms, and the functional proteins by which they do this, are not clear. In order to explore one such protein, we developed a 2H5-F3 monoclonal antibody (2H5-F3 mAb) through its binding to bovine M cells, and identified the antibody reactive molecule as cyclophilin A (Cyp-A). The localization patterns of Cyp-A were very similar to the localization pattern of cytokeratin (CK) 18-positive M cells. Cyp-A was identified at the luminal surface of CK18-positive M cells in bovine jejunal and ileal FAE. The membranous localization of Cyp-A in the bovine intestinal cell line (BIE cells) increased as cells differentiated toward M cells, as determined by flow cytometry analysis. Additionally, BIE cells released Cyp-A to the extracellular space and the differentiation of BIE cells to M cells increased the secretion of Cyp-A, as determined by western blotting. Accordingly, Cyp-A may be localized in M cells in the small intestinal epithelium of cattle. The rise of the membranous localization and secretion of Cyp-A by differentiation toward M cells indicates that Cyp-A has an important role in the function of M cells. While Cyp-A of the M cell membrane may contribute to the uptake of viruses with peptidyl-prolyl cis-trans isomerase activity, in the extracellular space Cyp-A may work as a chemokine and contribute to the distribution of immuno-competent cells.
Insights
Cyclophilin A (Cyp-A) is identified as a key protein in bovine Microfold (M) cells, crucial for mucosal immunity. Increased Cyp-A localization and secretion during M cell differentiation suggest its role in microbial uptake and immune cell distribution.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- Microfold (M) cells in Peyer's patches are vital for mucosal immune responses via transcytosis of microorganisms.
- The precise mechanisms and proteins involved in M cell microbial uptake remain unclear.
- Understanding M cell function is critical for developing targeted mucosal immunotherapies.
Purpose of the Study:
- To identify functional proteins involved in M cell-mediated microbial uptake.
- To investigate the role of cyclophilin A (Cyp-A) in bovine M cell function.
- To elucidate the localization and secretion patterns of Cyp-A during M cell differentiation.
Main Methods:
- Development of a monoclonal antibody (2H5-F3 mAb) targeting bovine M cells.
- Identification of the antibody's target molecule as cyclophilin A (Cyp-A).
- Flow cytometry and western blotting to analyze Cyp-A localization and secretion in M cells and BIE cells.
Main Results:
- Cyclophilin A (Cyp-A) was identified as a molecule reactive with the 2H5-F3 mAb on bovine M cells.
- Cyp-A demonstrated similar localization patterns to cytokeratin 18 (CK18)-positive M cells in the intestinal epithelium.
- Membranous localization and extracellular secretion of Cyp-A increased significantly as BIE cells differentiated into M cells.
Conclusions:
- Cyclophilin A (Cyp-A) is localized in M cells within the bovine small intestinal epithelium.
- The increased membranous presence and secretion of Cyp-A suggest a significant role in M cell function, including microbial uptake and immune cell interaction.
- Cyp-A may mediate viral uptake via its peptidyl-prolyl cis-trans isomerase activity and act as a chemokine in the extracellular space.
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