scholarly journals Intestinal Epithelial Cell-Derived CD83 Contributes to Regulatory T-Cell Generation and Inhibition of Food Allergy

2021 ◽  
pp. 1-11
Author(s):  
Yong Yu ◽  
Qiao-Ruo Jin ◽  
Yang Mi ◽  
Jiang-Qi Liu ◽  
Zhi-Qiang Liu ◽  
...  

The mechanism of generation of antigen-specific regulatory T cells (Treg) is not fully understood yet. This study aimed to investigate the role of intestinal epithelial cell (IEC)-derived CD83 in the Treg generation in the intestine. In this study, the role of CD83 in the generation of Tregs was assessed in a cell-culture model and a food allergy (FA) mouse model. We found that mouse IECs expressed CD83; its levels were markedly lower in sensitized mice. Mice with CD83-deficient IECs failed to induce Tregs in the intestine. CD83 promoted the transforming growth factor-β-inducible early gene 1 (TIEG1) expression in CD4<sup>+</sup> T cells. Toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) complex mediated the effects of CD83 on the expression of TIEG1. Activation of the CD83/TLR4/MD-2/TIEG1 promoted the Treg generation. Concomitant administration of CD83 and specific antigens, but not either one alone, efficiently inhibited experimental FA via inducing the Treg generation in the intestine. In Conclusion, IEC expresses CD83 that is low in sensitized mice. Concomitant administration of CD83 and specific antigens efficiently inhibits FA in a murine model via inducing Tregs in the intestine. The data suggest that CD83 has translation potential in the treatment of FA.

Blood ◽  
1970 ◽  
Vol 35 (1) ◽  
pp. 94-103 ◽  
Author(s):  
R. BEN DAWSON ◽  
SHEILA RAFAL ◽  
LEWIS R. WEINTRAUB

Abstract Heme from ingested hemoglobin—59Fe is taken into the epithelial cell of the small intestinal mucosa of the dog and the 59Fe subsequently appears in the plasma bound to transferrin. A substance was demonstrated in homogenates of the mucosa which releases iron from a hemoglobin substrate in vitro. Thus: (1) The addition of catalase to the mucosal homogenate reduces the "heme-splitting" reaction. In contrast, sodium azide, a catalase inhibitor, potentiates the reaction. This suggests that a peroxide generating system participates in the "heme-splitting" reaction. (2) Xanthine oxidase, an enzyme present in the intestinal epithelial cell, produces H2O2 by oxidation of its substrate. The addition of allopurinol, a xanthine oxidase inhibitor, to the intestinal mucosal homogenate diminishes the "heme-splitting" reaction. (3) Fractionation of the 50,000 Gm. supernatant of the mucosal homogenate on a G-200 Sephadex column shows the "heme-splitting" activity to have the same elution volume as xanthine oxidase, indicating a similar molecular weight. (4) The addition of a mucosal homogenate to a xanthine substrate results in the production of uric acid. These data suggest that xanthine oxidase in the intestinal epithelial cell is important in the release of iron from absorbed heme. The enzyme mediates the "heme-splitting" reaction by the generation of peroxides which, in turn, oxidize the alpha-methene bridge of the heme ring releasing iron and forming biliverdin.


2001 ◽  
Vol 266 (2) ◽  
pp. 311-322 ◽  
Author(s):  
Mitsuo Shimizu ◽  
Kazunobu Minakuchi ◽  
Ayako Tsuda ◽  
Takachika Hiroi ◽  
Noboru Tanaka ◽  
...  

2002 ◽  
Vol 169 (8) ◽  
pp. 4417-4422 ◽  
Author(s):  
Kathleen B. Madden ◽  
Lucia Whitman ◽  
Carolyn Sullivan ◽  
William C. Gause ◽  
Joseph F. Urban ◽  
...  

2003 ◽  
Vol 124 (4) ◽  
pp. A83
Author(s):  
Matthieu Allez ◽  
Jens Brinnes ◽  
Ling Shao ◽  
Iris Dotan ◽  
Atsushi Nakazawa ◽  
...  

2008 ◽  
Vol 295 (2) ◽  
pp. G273-G284 ◽  
Author(s):  
Takashi Kanaya ◽  
Kohtaro Miyazawa ◽  
Ikuro Takakura ◽  
Wataru Itani ◽  
Kouichi Watanabe ◽  
...  

M cells are a kind of intestinal epithelial cell in the follicle-associated epithelium of Peyer's patches. These cells can transport antigens and microorganisms into underlying lymphoid tissues. Despite the important role of M cells in mucosal immune responses, the origin and mechanisms of differentiation as well as cell death of M cells remain unclear. To clarify the mechanism of M cell differentiation, we established a novel murine intestinal epithelial cell line (MIE) from the C57BL/6 mouse. MIE cells grow rapidly and have a cobblestone morphology, which is a typical feature of intestinal epithelial cells. Additionally, they express cytokeratin, villin, cell-cell junctional proteins, and alkaline phosphatase activity and can form microvilli. Their expression of Musashi-1 antigen indicates that they may be close to intestinal stem cells or transit-amplifying cells. MIE cells are able to differentiate into the M cell lineage following coculture with intestinal lymphocytes, but not with Peyer's patch lymphocytes (PPL). However, PPL costimulated with anti-CD3/CD28 MAbs caused MIE cells to display typical features of M cells, such as transcytosis activity, the disorganization of microvilli, and the expression of M cell markers. This transcytosis activity of MIE cells was not induced by T cells isolated from PPL costimulated with the same MAbs and was reduced by the depletion of the T cell population from PPL. A mixture of T cells treated with MAbs and B cells both from PPL led MIE cells to differentiate into M cells. We report here that MIE cells have the potential ability to differentiate into M cells and that this differentiation required activated T cells and B cells.


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