Cyclophilin A is a new M cell marker of bovine intestinal epithelium
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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.
KeywordsM cell Follicle associated epithelium Peyer’s patch Bovine intestinal epithelium Cyclophilin A
T.H., S.S. and H.A. conception and design of research; T.H., S.S., Y.N., S.T., H.W., X.C., K.W., S.O. and H.A. performed experiments; T.H. and S.S. analyzed data; T.H., S.S., K.W., S.O., H.K., T.N. and H.A. interpreted results of experiments; T.H. and S.S. prepared figures; T.H., S.S., and S.T. drafted manuscript; T.H., S.S., M.T.R. and H.A. edited and revised the manuscript; H.A. approved final version of manuscript.
This study was supported by a Grant-in-Aid for Scientific Research (B) (no. 15H04586) and a Grant-in-Aid for Exploratory Research (no. 26660217) from the Japan Society for the Promotion of Science (JSPS).
Compliance with ethical standards
No conflicts of Interest, financial or otherwise, are declared by the author(s).
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