The role of nicotinic receptors in B-lymphocyte development and activation

Skok, Maryna; Grailhe, Régis; Agenès, Fabien; Jp, Changeux

doi:10.1016/j.lfs.2007.02.005

Cited by 84 publications

(60 citation statements)

References 17 publications

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“…The nAChRs in immune cells have been identified where they play an important role in cholinergic control of immunity (Kawashima and Fujii, 2003;Skok et al, 2007). To determine the expression of a4 nAChRs, we isolated a4-expressing cells (a4 1 ) from the blood ICF of mice.…”

Section: Resultsmentioning

confidence: 99%

“…We used glyceraldehyde 3-phosphate dehydrogenase as a loading control. Studies have indicated an effect of chronic nicotine on cytokine and Ab production (Song et al, 1999;Skok et al, 2007). We examined the effects of a 6-day (sustained) nicotine treatment (0.5-1.0 mg/kg) in mice.…”

Section: Resultsmentioning

confidence: 99%

“…In mice lacking the a4 nAChR (a4 2/2 ), nicotine binding appears to be all but abolished in several organs (Marubio et al, 1999). The a4 nAChRs are well expressed in immune cells, including T and B lymphocytes, and have been implicated in regulating cytokine release as well as antibody production (Skok et al, 2007). Indeed, a4 2/2 mice have been found to exhibit abnormalities in lymphocyte development and maturation (Skok et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Theα4 Nicotinic Receptor Promotes CD4⁺T-Cell Proliferation and a Helper T-Cell Immune Response

et al. 2013

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Smoking is a common addiction and a leading cause of disease. Chronic nicotine exposure is known to activate nicotinic acetylcholine receptors (nAChRs) in immune cells. We demonstrate a novel role for a4 nAChRs in the effect of nicotine on T-cell proliferation and immunity. Using cell-based sorting and proteomic analysis we define an a4 nAChR expressing helper T-cell population (a4 1 CD3 1 CD4 1 ) and show that this group of cells is responsive to sustained nicotine exposure. In the circulation, spleen, bone marrow, and thymus, we find that nicotine promotes an increase in CD31 CD4 1 cells via its activation of the a4 nAChR and regulation of G protein subunit o, G protein regulated-inducer of neurite outgrowth, and CDC42 signaling within T cells. In particular, nicotine is found to promote a helper T cell 2 adaptive immunologic response within T cells that is absent in a4 2 / 2 mice. We thus present a new mechanism of a4 nAChR signaling and immune regulation in T cells, possibly accounting for the effect of smoking on the immune system.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Theα4 Nicotinic Receptor Promotes CD4⁺T-Cell Proliferation and a Helper T-Cell Immune Response

et al. 2013

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“…The ␣7 nAChR is a homopentameric nAChR present on macrophages (2), T cells (3,4), and B cells (5). It was shown that activation of this receptor on macrophages reduces secretion of the proinflammatory cytokines TNF-␣, IL-1␤, and IL-6, whereas production of anti-inflammatory cytokines such as IL-10 is not affected (6).…”

mentioning

confidence: 99%

Activation of the Cholinergic Anti-Inflammatory System by Nicotine Attenuates Neuroinflammation via Suppression of Th1 and Th17 Responses

Nizri

Irony-Tur-Sinai

Lory

et al. 2009

The Journal of Immunology

261

230

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The α7 nicotinic acetylcholine receptor (nAChR) was recently described as an anti-inflammatory target in both macrophages and T cells. Its expression by immune cells may explain the epidemiological data claiming a negative link between cigarette smoking and several inflammatory diseases. In this study, we determined the immunological effects of α7 nAChR activation by nicotine. Our results indicate that the α7 nAChR is expressed on the surface of CD4+ T cells and that this expression is up-regulated upon immune activation. Nicotine reduced T cell proliferation in response to an encephalitogenic Ag, as well as the production of Th1 (TNF-α and IFN-γ) and Th17 cytokines (IL-17, IL-17F, IL-21, and IL-22). IL-4 production was increased in the same setting. Attenuation of the Th1 and Th17 lineages was accompanied by reduced T-bet (50%) and increased GATA-3 (350%) expression. Overall, nicotine induced a shift to the Th2 lineage. However, α7−/−-derived T cells were unaffected by nicotine. Furthermore, nicotine reduced NF-κB-mediated transcription as measured by IL-2 and IκB transcription. In vivo, administration of nicotine (2 mg/kg s.c.) suppressed the severity of CD4+ T cell-mediated disease experimental autoimmune encephalomyelitis. α7−/− mice were refractory to nicotine treatment, although disease severity in those animals was reduced, due to impairment in Ag presentation. Accordingly, CD4+ and CD11b+ cells infiltration into the CNS, demyelination, and axonal loss were reduced. Our data implicate a role for the α7 nAChR in immune modulation and suggest that α7 nAChR agonists may be effective in the treatment of inflammatory disorders.

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“…It is now well established that receptors for the parasympathetic mediator acetylcholine (ACh) and the sympathetic mediator norepinephrine (NE) are expressed on various immune cells such as macrophages, neutrophils, and lymphocytes [10][11][12]. For instance, activation of the ACh receptor on human macrophages exposed to bacterial lipopolysaccharide (LPS) significantly attenuates the release of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1β, IL-6, and IL-18, but not the production of anti-inflammatory cytokines (such as IL-10) [13].…”

Section: Introductionmentioning

confidence: 99%

Neuro-endocrine-immune Crosstalk and Implications for Cancer Therapy

Dronca¹,

Markovic²,

Holtan³

et al. 2011

J Cel Sci Therapy

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The role of nicotinic receptors in B-lymphocyte development and activation

Cited by 84 publications

References 17 publications

Theα4 Nicotinic Receptor Promotes CD4⁺T-Cell Proliferation and a Helper T-Cell Immune Response

Theα4 Nicotinic Receptor Promotes CD4⁺T-Cell Proliferation and a Helper T-Cell Immune Response

Activation of the Cholinergic Anti-Inflammatory System by Nicotine Attenuates Neuroinflammation via Suppression of Th1 and Th17 Responses

Neuro-endocrine-immune Crosstalk and Implications for Cancer Therapy

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The role of nicotinic receptors in B-lymphocyte development and activation

Cited by 84 publications

References 17 publications

Theα4 Nicotinic Receptor Promotes CD4+T-Cell Proliferation and a Helper T-Cell Immune Response

Theα4 Nicotinic Receptor Promotes CD4+T-Cell Proliferation and a Helper T-Cell Immune Response

Activation of the Cholinergic Anti-Inflammatory System by Nicotine Attenuates Neuroinflammation via Suppression of Th1 and Th17 Responses

Neuro-endocrine-immune Crosstalk and Implications for Cancer Therapy

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Product

Resources

About

Theα4 Nicotinic Receptor Promotes CD4⁺T-Cell Proliferation and a Helper T-Cell Immune Response

Theα4 Nicotinic Receptor Promotes CD4⁺T-Cell Proliferation and a Helper T-Cell Immune Response