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Distinct Roles of ?7 nAChRs in Antigen-Presenting Cells and CD4⁺ T Cells in the Regulation of T Cell Differentiation.

ABSTRACT: It is now apparent that immune cells express a functional cholinergic system and that ?7 nicotinic acetylcholine receptors (?7 nAChRs) are involved in regulating T cell differentiation and the synthesis of antigen-specific antibodies and proinflammatory cytokines. Here, we investigated the specific function ?7 nAChRs on T cells and antigen presenting cells (APCs) by testing the effect of GTS-21, a selective ?7 nAChR agonist, on differentiation of CD4⁺ T cells from ovalbumin (OVA)-specific TCR transgenic DO11.10 mice activated with OVA or OVA peptide_323-339 (OVAp). GTS-21 suppressed OVA-induced antigen processing-dependent development of CD4⁺ regulatory T cells (Tregs) and effector T cells (Th1, Th2, and Th17). By contrast, GTS-21 up-regulated OVAp-induced antigen processing-independent development of CD4⁺ Tregs and effector T cells. GTS-21 also suppressed production of IL-2, IFN-?, IL-4, IL-17, and IL-6 during OVA-induced activation but, with the exception IL-2, enhanced their production during OVAp-induced activation. In addition, during antigen-nonspecific, APC-independent anti-CD3/CD28 antibody-induced CD4⁺ polyclonal T cell activation in the presence of respective polarizing cytokines, GTS-21 promoted development of all lineages, which indicates that GTS-21 also acts via ?7 nAChRs on T cells. These results suggest 1) that ?7 nAChRs on APCs suppress CD4⁺ T cell activation by interfering with antigen presentation through inhibition of antigen processing; 2) that ?7 nAChRs on CD4⁺ T cells up-regulate development of Tregs and effector T cells; and that ?7 nAChR agonists and antagonists could be potentially useful agents for immune response modulation and enhancement.

SUBMITTER: Mashimo M

PROVIDER: S-EPMC6554293 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Distinct Roles of α7 nAChRs in Antigen-Presenting Cells and CD4<sup>+</sup> T Cells in the Regulation of T Cell Differentiation.

Mashimo Masato M Komori Masayo M Matsui Yuriko Y YY Murase Mami X MX Fujii Takeshi T Takeshima Shiori S Okuyama Hiromi H Ono Shiro S Moriwaki Yasuhiro Y Misawa Hidemi H Kawashima Koichiro K

Frontiers in immunology 20190531

It is now apparent that immune cells express a functional cholinergic system and that α7 nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating T cell differentiation and the synthesis of antigen-specific antibodies and proinflammatory cytokines. Here, we investigated the specific function α7 nAChRs on T cells and antigen presenting cells (APCs) by testing the effect of GTS-21, a selective α7 nAChR agonist, on differentiation of CD4<sup>+</sup> T cells from ovalbumin (OVA)-spec ...[more]

PMID: 31214160

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Project description:In leishmaniasis, the protective immunity is largely mediated by proinflammatory cytokine producing abilities of T cells and an efficient parasite killing by phagocytic cells. Notwithstanding a substantial progress that has been made during last decades, the mechanisms or factors involved in establishing protective immunity against Leishmania are not identified. In ancient Indian literature, metallic "bhasma," particularly that of "swarna" or gold (fine gold particles), is indicated as one of the most prominent metal-based therapeutic medicine, which is known to impart protective and curative properties in various health issues. In this work, we elucidated the potential of swarna bhasma (SB) on the effector properties of phagocytes and antigen-activated CD4+ T cells in augmenting the immunogenicity of L. donovani antigens. The characterization of SB revealing its shape, size, composition, and measurement of cytotoxicity established the physiochemical potential for its utilization as an immunomodulator. The activation of macrophages with SB enhanced their capacity to produce nitric oxide and proinflammatory cytokines, which eventually resulted in reduced uptake of parasites and their proliferation in infected cells. Further, in Leishmania-infected animals, SB administration reduced the generation of IL-10, an anti-inflammatory cytokine, and enhanced pro-inflammatory cytokine generation by antigen activated CD4+ T cells with increased frequency of double (IFNγ+/TNFα+) and triple (IFNγ+TNFα+IL-2+) positive cells and abrogated disease pathogeneses at the early days of infection. Our results also suggested that cow-ghee (A2) emulsified preparation of SB, either alone or with yashtimadhu, a known natural immune modulator which enhances the SB's potential in enhancing the immunogenicity of parasitic antigens. These findings suggested a definite potential of SB in enhancing the effector functions of phagocytes and CD4+ T cells against L. donovani antigens. Therefore, more studies are needed to elucidate the mechanistic details of SB and its potential in enhancing vaccine-induced immunity.

Dataset Information

Distinct Roles of ?7 nAChRs in Antigen-Presenting Cells and CD4⁺ T Cells in the Regulation of T Cell Differentiation.

Publications

Distinct Roles of α7 nAChRs in Antigen-Presenting Cells and CD4<sup>+</sup> T Cells in the Regulation of T Cell Differentiation.

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Dataset Information

Distinct Roles of ?7 nAChRs in Antigen-Presenting Cells and CD4+ T Cells in the Regulation of T Cell Differentiation.

Publications

Distinct Roles of α7 nAChRs in Antigen-Presenting Cells and CD4<sup>+</sup> T Cells in the Regulation of T Cell Differentiation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Distinct Roles of ?7 nAChRs in Antigen-Presenting Cells and CD4⁺ T Cells in the Regulation of T Cell Differentiation.