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Differential expression of vasoactive intestinal polypeptide receptor 1 and 2 mRNA in murine intestinal T lymphocyte subtypes
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
2001 (English)In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 13, no 9, 818-825 p.Article in journal (Refereed) Published
Abstract [en]

Neuropeptides may exert a variety of effects on the immune cells at both systemic and mucosal immune sites. The immunoregulatory properties refer to the ability of physiological signals and pathways to influence various immune functions. Vasoactive intestinal polypeptide (VIP), a neuropeptide present in high concentration in gut, was studied for its production and receptor expression in intraepithelial and lamina propria T lymphocytes of mouse intestine. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, it was demonstrated that VIP receptor 1 (VIPR1) was constantly expressed in intraepithelial and lamina propria T lymphocytes from both small and large intestine. In contrast, VIPR2 was identified only in T cells from small intestine. Further studies on purified subpopulations of T lymphocytes indicated the existence of VIPR2 in CD8(+) T cells, but not CD4(+) and CD4CD8 double negative T cells, although all these three subpopulations displayed VIPR1. In addition, VIPR1 mRNA was detected in splenic T lymphocytes, but no signal was obtained for VIPR2 mRNA, even after stimulation of the cells with anti-CD3(epsilon)-chain mAb, phorbol 12-myristate 13-acetate (PMA) and/or VIP. The presence of VIP receptor(s) on intestinal T lymphocytes was supported by the detection of VIP on the cell surface using dual colour immunoflowcytometry. In-vitro treatment with VIP resulted in a tendency towards an increased size of the VIP immunoreactive T cell population and significantly enhanced the average immunofluorescence intensity of the surface labelling. This indicates that the receptors are partially occupied by locally produced VIP in vivo and that more peptide molecules can be bound on the lymphocytes when needed, released and accumulated in higher concentration at the action sites. We failed to detect the expression of VIP mRNA in T lymphocytes, from either intestine or spleen. These observations support that VIP may be an important immune modulator in gut acting through specific receptors on T lymphocytes. The differential mRNA expression of VIP receptor subtypes in cells with different phenotypes and in different immune compartments may suggest diverse regulatory roles of the neuropeptide in immune responses.

Place, publisher, year, edition, pages
2001. Vol. 13, no 9, 818-825 p.
Keyword [en]
vasoactive intestinal polypeptide; receptor; intestinal lymphocyte(s); mouse
National Category
Neurosciences Endocrinology and Diabetes
URN: urn:nbn:se:umu:diva-68059DOI: 10.1046/j.1365-2826.2001.00703.xPubMedID: 11578532OAI: diva2:615650
Available from: 2013-04-11 Created: 2013-04-11 Last updated: 2013-06-20Bibliographically approved
In thesis
1. An experimental study on the interaction between the neuro-endocrine and immune systems in the gastrointestinal tract
Open this publication in new window or tab >>An experimental study on the interaction between the neuro-endocrine and immune systems in the gastrointestinal tract
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The mucosa lining of the gastrointestinal (GI) tract is in immediate contact with food nutrients to allow a rapid and efficient digestion and absorption and at the same time protects against the incessant risk of attack from pathogenic microbes. Maintenance of normal physiological activities in the GI tract is dependent on a number of regulatory interactions between the nervous, endocrine, and immune systems, as well as environmental and genetic factors. Impaired nervous and/or endocrine systems may endanger mucosal immunity and thereby increase the susceptibility to infectious agents, elicit an uncontrolled inflammatory response and cause a failure of immune surveillance. Aberrant immune functions may also lead to an apparent neuro-endocrine disturbance. A better understanding of the neuro-endocrine immunomodulation in the GI tract and its influence on the inflammatory process, therefore, will hold the promise of novel strategy to the treatment of immunologically and/or neuro-endocrinologically mediated diseases with the use of appropriate regulatory substances.

In this thesis, the neuro-endocrine system and its interaction(s) with the immune system in the GI tract were studied using mouse models combined with immunological and molecular biological techniques (e.g. immunomorphometry, quantitative RT-PCR). The following could be concluded:

1) Vagus nerves are fundamental to the enteric neuro-endocrine system. Frequencies and morphology of several types of endocrine cells and tissue levels of neuropeptides along the GI tract were significantly changed by vagotomy.

2) The local enteric neuro-endocrine system may have important influences on bowel inflammation. Polypeptide YY (PYY) cells and tissue levels of PYY, substance P (SP) and vasoactive intestinal polypeptide (VIP) were dramatically decreased in the inflamed colon of IL-2-/- mice as compared to the health IL-2+/- and IL-2+/+ controls.

3) Notably, IL-2 deficiency per se caused marked neuro-endocrine alterations in the gut. The volume densities of enteroglucagon-, serotonin-cells and SP-, VIP- or total myenteric nerves were lower in IL-2+/- and IL-2-/- mice as compared to the wild type. The normally occurring age related neuro-endocrine changes were also absent in mice with no (IL-2-/- mice) or reduced levels of IL-2 (IL-2+/- mice).

4) VIP generally exerted immunosuppressive effects. The magnitude of the effect differed with T cells in different compartments. Proliferation in response to polyclonal T cell activators was significantly down-regulated by VIP in splenic but not intestinal T lymphocytes. Cytokine production was also affected. Expression of mRNAs for interleukin-2 (IL-2), the Th1 cytokine interferon-γ (IFN-γ), and the Th2 cytokine IL-4 in activated small intestinal lamina propria and splenic T cells was inhibited by VIP in a dose dependent manner. In contrast, the inhibitory action of VIP on cytokine production was much less pronounced in intestinal intraepithelial T lymphocytes in which only IFN-γ mRNA expression was reduced.

5) The effects of VIP on lymphocytes are most probably receptor mediated. Intestinal T cells were shown to bind VIP. T cells in both small and large intestine as well as spleen had the mRNA expression for VIP-receptor 1. It was expressed in all T cell subtypes tested i.e. CD4+ , CD8+, and CD4-CD8-CD3+ cells. Interestingly, VIP receptor 2 mRNA was only found in CD8+ lymphocytes of small intestine. This indicates a functional diversity and specificity of VIP in immune modulation.

6) SP may act as an autocrine as well as a paracrine immunoregulatory agent in intestinal mucosa. T cells from both the epithelium and lamina propria of small and large intestine were found to produce SP and at the same time express the SP receptor.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2001. 62 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 719
gastrointestinal tract, neuro-endocrine system, substance P, vasoactive intestinal polypeptide, vagus nerves, mucosal immune system, T lymphocytes, cytokines, inflammation, mouse
National Category
Neurology Endocrinology and Diabetes
urn:nbn:se:umu:diva-73364 (URN)91-7191-994-5 (ISBN)
Public defence
2001-03-15, Astrid Fagreussalen A103, Norrlands universitetssjukhus, Umeå, 09:00
Available from: 2013-06-20 Created: 2013-06-20 Last updated: 2013-06-20Bibliographically approved

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