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Title: Intraepithelial lymphocytes express junctional molecules in murine small intestine

Abstract

Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), {beta}-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and Peyer's patches did not. {gamma}{delta} IEL showed higher level of these expressions than {alpha}{beta} IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC.

Authors:
 [1];  [2];  [2];  [3];  [4]
  1. Parasitic Diseases Unit, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan). E-mail: INAGAKI@med.miyazaki-u.ac.jp
  2. Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)
  3. Molecular Microbiology Group, Center of Molecular Biosciences, University of the Ryukyus, Senbaru, Nishihara, Okinawa 903-0213 (Japan)
  4. Parasitic Diseases Unit, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)
Publication Date:
OSTI Identifier:
20710794
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 331; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2005.04.025; PII: S0006-291X(05)00772-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; LIVER; LYMPH NODES; LYMPHOCYTES; PROTEINS; SMALL INTESTINE; SPLEEN; THYMUS

Citation Formats

Inagaki-Ohara, Kyoko, Sawaguchi, Akira, Suganuma, Tatsuo, Matsuzaki, Goro, and Nawa, Yukifumi. Intraepithelial lymphocytes express junctional molecules in murine small intestine. United States: N. p., 2005. Web. doi:10.1016/j.bbrc.2005.04.025.
Inagaki-Ohara, Kyoko, Sawaguchi, Akira, Suganuma, Tatsuo, Matsuzaki, Goro, & Nawa, Yukifumi. Intraepithelial lymphocytes express junctional molecules in murine small intestine. United States. doi:10.1016/j.bbrc.2005.04.025.
Inagaki-Ohara, Kyoko, Sawaguchi, Akira, Suganuma, Tatsuo, Matsuzaki, Goro, and Nawa, Yukifumi. 2005. "Intraepithelial lymphocytes express junctional molecules in murine small intestine". United States. doi:10.1016/j.bbrc.2005.04.025.
@article{osti_20710794,
title = {Intraepithelial lymphocytes express junctional molecules in murine small intestine},
author = {Inagaki-Ohara, Kyoko and Sawaguchi, Akira and Suganuma, Tatsuo and Matsuzaki, Goro and Nawa, Yukifumi},
abstractNote = {Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), {beta}-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and Peyer's patches did not. {gamma}{delta} IEL showed higher level of these expressions than {alpha}{beta} IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC.},
doi = {10.1016/j.bbrc.2005.04.025},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 331,
place = {United States},
year = 2005,
month = 6
}
  • The proliferative kinetics of the intraepithelial lymphocytes (IL) of the mouse intestine have been evaluated. By inducing mitotic arrest it was found that large IL--constituting about 50% of the IL--showed a mitotic rate of 2.3. Autoradiographic results obtained after two different schedules of /sup 3/H-thymidine injections showed that 30% of the large IL were in DNA synthesis, and that the large IL were renewed at a rate comparable to that of blast cells from Peyer's patches, mesenteric lymph nodes and thoracic duct lymph. The small IL were renewed very rapidly compared to small lymphocytes of peripheral lymphoid tissues, although smallmore » lymphocytes with lifespans of several weeks were also present in the epithelial sheet. By the use of intestinal perfusion, in vivo, it was estimated that the loss of lymphocytes from intestinal villi into the lumen of the gut was negligible, and it is concluded that the most probable kinetic model for the majority of IL is: B and T lymphoblasts invade the epithelium and undergo mitosis. B lymphoblasts give rise predominantly to plasma cells, and T lymphoblasts give rise to small lymphocytes--probably long-lived--which reenter the circulation.« less
  • The kinetics of lymphoid cells within the epithelium of the small gut has been studied in various thymus-deprived mice and in antigen-deprived mice by the use of /sup 3/H-thymidine injections and radioautography. In thymus-deprived mice--including adult thymectomized, thymectomized and irradiated, neonatally thymectomized, and nude mice--and in germ-free mice decreased numbers of intraepithelial lymphocytes (IL) were found. On the other hand, the radioautographic results indicated that the remaining IL populations included both newly formed and long-lived lymphoid cells in the same percentages as found in sham-operated controls and normal mice. It is concluded that although the presence of the thymus andmore » the antigen content of the gut is of importance to the maintenance of the numbers of cells in the lymphoid populations of the intestinal wall, the basic kinetics of these cell populations are preserved in deprived mice.« less
  • Murine intestinal intraepithelial lymphocytes (IELs) can be classified according to expression of a CD43 glycoform recognized by the S7 monoclonal antibody. In this study, we examined the response of S7+ and S7- IELs in mice during acute reovirus serotype 3 (Dearing strain) infection, which was confirmed by virus-specific real-time PCR. In vivo proliferation increased significantly for both S7- and S7+ IELs on day 4 post-infection as determined by BrdU incorporation; however, expression of the inducible costimulatory (ICOS) molecule, which peaked on day 7 post-infection, was upregulated on S7+ CD4+ T cells, most of which were CD4+8- IELs. In vitro ICOSmore » stimulation by syngeneic peritoneal macrophages induced IFN-{gamma} secretion from IELs from day 7 infected mice, and was suppressed by treatment with anti-ICOS mAb. Additionally, IFN-{gamma} mRNA increased in CD4+ IELs on day 6 post-infection. These findings indicate that S7- and S7+ IELs are differentially mobilized during the immune response to reovirus infection; that the regulated expression of ICOS is associated with S7+ IELs; and that stimulation of IELs through ICOS enhances IFN-{gamma} synthesis during infection.« less
  • Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4{sup +} IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4{sup +} IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4{sup +} IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs)more » and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4{sup +} IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4{sup +} LPLs and primed splenic CD4{sup +} T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4{sup +} IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo.« less
  • A portion of jejunum in C3H/HeJ mice was irradiated in situ with 250 kV X-rays, and the resulting elastic stiffness increase was used as an assay of chronic fibrotic injury. With data from this assay dose-response curves were evaluated with early- and late-appearing chronic intestinal injuries in two experiments. (1) After split-dose treatment with an interfraction interval of 0.0, 0.25, 0.5, 1.0, 2, 4 or 24 h, the asymptotic dose-recovery ratios in assays at 2-3 weeks and at 4 months were statistically similar, R = 1.34 (95% confidence limits: 1.29-1.39) with t{sub {1/2}} = 0.75 h (0.48-1.17), and R =more » 1.36 (1.31-1.42) with t{sub {1/2}} = 0.49 h (0.21-0.86), respectively, although the slopes of the dose-response curves for the early and late assay differed significantly. (2) Mice received 2, 3, 4, 5, 10 or 15 equal X-ray fractions in 5 days with interfraction intervals of at least 5.5-6 h. The data from the dose responses were used in either of two analyses of variance for calculating {alpha}/{beta} values. Using slopes in transformed F{sub e} plots, {alpha}/{beta} was 8.5 Gy (6.1-12.5) for the assay at 2-3 weeks and 3.6 Gy (2.4-5.4) at 4 months. Using these and other data we argue that assay at the two times measured separate fibrotic responses to injuries to the small intestine, namely, a rapidly appearing consequential late effect that had the same {alpha}/{beta} value as for crypt microcolony assays because it was a sequela of acute inflammation after transient loss of mucosal epithelial integrity after crypt sterilization, and a lower-threshold primary or true late effect with a lower {alpha}/{beta} value, which progressively masked the consequential injury. 25 refs., 7 figs., 2 tabs.« less