Nicotine alters the biological activities of developing mouse bone marrow-derived dendritic cells (DCs)

Nouri-Shirazi, Mahyar; Tinajero, R.; Guinet, Elisabeth

doi:10.1016/j.imlet.2007.02.005

Cited by 70 publications

(74 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At the same time, levels of IL-10 were reduced, whereas levels of IL-4, the main Th2 cytokine, were increased. Analysis of specific TFs responsible for Th lineage differentiation supported a shift toward the Th2 lineage, as previously reported (37,38): treatment reduced transcription of T-bet and increased the level of GATA-3. However, the Th17-related TFs, ROR-␥T and ROR-␣, were unaffected, despite the decreased production of Th17-related cytokines.…”

Section: Discussionsupporting

confidence: 83%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 83%

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

View full text Add to dashboard Cite

show abstract

“…Nicotine has been demonstrated to have a number of effects on immune cell function, most of which seem to be inhibitory (Guinet et al, 2004;Kalra et al, 2004;Middlebrook et al, 2002;Nouri-Shirazi et al, 2007). The current study identifies nicotine as the likely primary constituent in cigarette smoke involved in cigarette smoke-induced COX-2 and PGE 2 production by maturing DCs.…”

Section: Discussionmentioning

confidence: 73%

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Vassallo

Kroening

Parambil

et al. 2008

Molecular Immunology

100

View full text Add to dashboard Cite

Chronic airway inflammation is a cardinal feature of chronic obstructive pulmonary disease (COPD), a destructive cigarette smoke-induced lung disease. Although it is apparent that dendritic cells (DCs) are an important constituent of the chronic inflammatory cell influx found in airways of COPD patients, the functional roles of DCs in the pathogenesis of smoking-induced emphysema are unknown. We postulated that DCs activated by cigarette smoke constituents directly participate in the chronic inflammation that characterizes COPD airways. Concordant with this hypothesis, we observed that incubation of DCs with cigarette smoke extract (CSE), and chronic exposure of mice to cigarette smoke, both augmented the generation of neutrophilic chemokines by immature and lipopolysaccharide (LPS) or CD40L-matured DCs. The generation of interleukin-8 (CXCL8/IL-8) by human DCs conditioned with CSE was suppressed by the antioxidant n-acetyl cysteine (NAC), implying the involvement of oxidant sensitive pathways as a primary mechanism involved in the enhanced CXCL8/IL-8 generation. Cigarette smoke extract and nicotine also augment the production of secreted prostaglandin E 2 and intracellular cyclooxygenase-2 (COX-2) in maturing DCs. Whereas NAC suppressed production of CXCL8 by CSEconditioned DCs, it augmented production of PGE 2 and cellular COX-2 levels in maturing DCs. These studies indicate that the stimulation of DCs by cigarette smoke-induced oxidative stress and nicotine promote the generation of pro-inflammatory responses that promote chronic inflammation in smokers. Certain pharmacologic strategies such as anti-oxidant therapy may be only partially effective in mitigating cigarette smoke-induced pro-inflammatory DC-mediated responses in smokers.

show abstract

“…We have reported (18,20,21) that both human and mouse DCs differentiated ex vivo in the presence of nicotine (henceforth called nicDCs) hardly support the differentiation of IFN-gsecreting Th1 cells, whereas they potently promote the differentiation of IL-4-secreting Th2 cells. To determine the causal relationship between nicotine-induced DC alterations in vivo and the diminished host response to immunization, we first examined whether administration of nicDCs pulsed with OVA protein and matured with LPS direct adequate Ag-specific immune responses in mice adoptively transferred with OVA-specific T cells.…”

Section: Administration Of Dcs Differentiated In the Presence Of Nicomentioning

confidence: 99%

“…We previously reported (18,20,21) that both human monocytederived DCs and mouse BM-derived myeloid DCs generated ex vivo in the presence of growth factors GM-CSF/IL-4 during nicotine exposure produce substantially less Th1-promoting cytokine IL-12 in response to the Th1-polarizing adjuvant LPS. Prior to establishing whether nicotine interferes with the immunobiology of developing DC subsets in vivo, including myeloid, lymphoid, and plasmacytoid DCs, we first evaluated the extent to which the presence of nicotine in the microenvironment would affect the ex vivo differentiation of BM DC precursors into DC subsets in response to FLT3 ligand, the key growth and differentiation factor for DC subsets in vivo (27)(28)(29) (Fig.…”

Section: Nicotine Exposure Impacts DC Subsets In Vivomentioning

confidence: 99%

“…The observed immunosuppression in smokers combined with the importance of DCs in maintaining immunity led us to study whether the biological activities of DCs are severely affected by exposure to nicotine. Our pioneering in vitro work (18)(19)(20)(21) revealed the nicotine-induced defects in the differentiation and biological activities of both human and mouse DCs differentiated ex vivo, particularly the ability to prime effector memory T cells as a possible mechanism for the depressed immune response reported in vaccinated smokers (7)(8)(9). In this study, we report that exposure to nicotine significantly diminishes the development of Ag-specific effector memory Th1 cells and Ab production, leading to poor host response to an otherwise protective and therapeutic vaccine.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Exposure to Nicotine Adversely Affects the Dendritic Cell System and Compromises Host Response to Vaccination

Nouri-Shirazi

Guinet

2012

The Journal of Immunology

View full text Add to dashboard Cite

The magnitude of Th1 cells response to vaccination is a critical factor in determining protection from clinical disease. Our previous in vitro studies suggested that exposure to the nicotine component of cigarette smoke skews the differentiation of both human and mouse dendritic cell (DC) precursors into atypical DCs (DCs differentiated ex vivo in the presence of nicotine) lacking parameters essential for the development of Th1-mediated immunity. In this study, we determined the causal relationship between nicotine-induced DC alterations and host response to vaccines. We show that animals exposed to nicotine failed to develop and maintain Ag-specific effector memory Th1 cells and Ab production to protein-based vaccine formulated with Th1 adjuvants. Accordingly, both prophylactic and therapeutic vaccines failed to protect and cure the nicotine-exposed mice from disease. More importantly, we demonstrate the nicotine-induced defects in the biological activities of in vivo DCs as an underlying mechanism. Indeed, i.v. administration of DCs differentiated in the presence of nicotine preferentially promoted the development of Ag-specific IL-4–producing effector cells in the challenged mice. In addition, DC subsets isolated from mice exposed to nicotine produced significantly less cytokines in response to Th1 adjuvants and inadequately supported the development of Ag-specific Th1 cells. Collectively, our studies suggest that nicotine-induced defects in the DC system compromises vaccine efficacy in smokers.

show abstract

Nicotine alters the biological activities of developing mouse bone marrow-derived dendritic cells (DCs)

Cited by 70 publications

References 53 publications

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

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

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Exposure to Nicotine Adversely Affects the Dendritic Cell System and Compromises Host Response to Vaccination

Contact Info

Product

Resources

About