Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells

Burchell, Jennifer; Wikström, Matthew E.; Stumbles, Philip A.; Sly, Peter D.; Turner, Debra J.

doi:10.1152/ajplung.00521.2007

Cited by 46 publications

(46 citation statements)

References 68 publications

(76 reference statements)

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“…A variety of rodent models have demonstrated this phenomenon, including passive exposure to aeroallergen before sensitization or chronic exposure to aeroallergen after sensitization, with Treg induction and activity implicated in the maintenance of tolerance in both cases (11)(12)(13)(14)(15)(16). In contrast, repeated inhalation of complex Ag extracts such as house dust mite leads to persistent inflammation and remodeling in some cases (17), presumably as a consequence of their inherent TLR or proteolytic activity.…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

“…In this study, we have examined aeroallergen-capture and CD4 + T cell activating activity of mouse AMDC subsets during the induction of inhalation tolerance to inhaled OVA using a multi-OVA aerosol exposure model in sensitized BALB/c mice (13). This model shares several features with other postsensitization models of inhalation tolerance developed in mice (15,16) and rats (14), including suppressed recruitment of effector CD4 + T cells and eosinophils into the airways and attenuated airways hyperresponsiveness through the promotion of Treg activity.…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

“…Sensitization and aerosol challenge protocol were as previously described (13). In brief, on days 0 and 14, mice received 20 mg OVA (Grade V chicken egg; Sigma-Aldrich, Sydney, NSW, Australia) in 200 mL 2.25 mg aluminum hydroxide (Serra, Germany) via the i.p.…”

Section: Sensitization and Aerosol Challenge Protocolmentioning

confidence: 99%

“…route. Commencing on day 21, mice received either a single 1% OVA aerosol (31 aero) or a total of 8 3 1% OVA aerosols over a 3-wk period delivered three times a week (multiaero) as described by Burchell et al (13). Control mice were sensitized to OVA and received endotoxin-free PBS aerosols.…”

Section: Sensitization and Aerosol Challenge Protocolmentioning

confidence: 99%

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Restricted Aeroallergen Access to Airway Mucosal Dendritic Cells In Vivo Limits Allergen-Specific CD4+ T Cell Proliferation during the Induction of Inhalation Tolerance

Fear

Burchell

Lai

et al. 2011

The Journal of Immunology

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Chronic innocuous aeroallergen exposure attenuates CD4+ T cell-mediated airways hyperresponsiveness in mice; however, the mechanism(s) remain unclear. We examined the role of airway mucosal dendritic cell (AMDC) subsets in this process using a multi-OVA aerosol-induced tolerance model in sensitized BALB/c mice. Aeroallergen capture by both CD11blo and CD11bhi AMDC and the delivery of OVA to airway draining lymph nodes by CD8α− migratory dendritic cells (DC) were decreased in vivo (but not in vitro) when compared with sensitized but nontolerant mice. This was functionally significant, because in vivo proliferation of OVA-specific CD4+ T cells was suppressed in airway draining lymph nodes of tolerized mice and could be restored by intranasal transfer of OVA-pulsed and activated exogenous DC, indicating a deficiency in Ag presentation by endogenous DC arriving from the airway mucosa. Bone marrow-derived DC Ag-presenting function was suppressed in multi-OVA tolerized mice, and allergen availability to airway APC populations was limited after multi-OVA exposure, as indicated by reduced OVA and dextran uptake by airway interstitial macrophages, with diffusion rather than localization of OVA across the airway mucosal surface. These data indicate that inhalation tolerance limits aeroallergen capture by AMDC subsets through a mechanism of bone marrow suppression of DC precursor function coupled with reduced Ag availability in vivo at the airway mucosa, resulting in limited Ag delivery to lymph nodes and hypoproliferation of allergen-specific CD4+ T cells.

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Section: Endritic Cells (Dc)mentioning

confidence: 99%

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Section: Sensitization and Aerosol Challenge Protocolmentioning

confidence: 99%

Section: Sensitization and Aerosol Challenge Protocolmentioning

confidence: 99%

See 2 more Smart Citations

Restricted Aeroallergen Access to Airway Mucosal Dendritic Cells In Vivo Limits Allergen-Specific CD4+ T Cell Proliferation during the Induction of Inhalation Tolerance

Fear

Burchell

Lai

et al. 2011

The Journal of Immunology

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“…Our laboratory recently developed a model of allergen-induced attenuation of airway hyperresponsiveness in the mouse (Burchell et al, 2009). We reported a significant increase in Treg(CD4 + 25 + foxP3 + ) cell numbers in the main conducting airways which was associated with suppression of AHR in both the airways and parenchymal tissue compartments of the respiratory system using the highly sensitive and accurate forced-oscillation technique to measure AHR as described above.…”

Section: Regulatory T Cells and Airways Hyperresponsiveness Attenuationmentioning

confidence: 99%

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

Burchell

Strickland

Stumbles

2010

Pharmacology & Therapeutics

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Airways hyperresponsiveness (AHR) is one of the major clinical features of allergic airways disease including allergic asthma, however the immunological mechanisms leading to the induction and regulation of this disorder are not fully understood. In this review we will summarise the evidence of a number of studies, principally in murine models of AHR, suggesting a central role for respiratory tract dendritic cells (RTDC) in the induction of AHR through the generation of lung-homing, allergen-specific effector T cells. We will also summarise the evidence supporting a role for regulatory T cells in the attenuation of AHR and will propose that, as a counterpoint to their capacity to induce AHR, RTDC may also play a role in the attenuation of AHR through the generation of regulatory T cells (Treg). A better understanding of the relationship between the physiological and immunological responses to allergen-induced AHR attenuation, and particularly the role of RTDC and Treg in this process, will be essential for the development of new treatments and therapies.

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Foxp3 Expressing Regulatory T-Cells in Allergic Disease

Nouri‐Aria

2009

Advances in Experimental Medicine and Biology

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Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells

Abstract: Burchell JT, Wikstrom ME, Stumbles PA, Sly PD, Turner DJ. Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells.

Cited by 46 publications

References 68 publications

Restricted Aeroallergen Access to Airway Mucosal Dendritic Cells In Vivo Limits Allergen-Specific CD4+ T Cell Proliferation during the Induction of Inhalation Tolerance

Restricted Aeroallergen Access to Airway Mucosal Dendritic Cells In Vivo Limits Allergen-Specific CD4+ T Cell Proliferation during the Induction of Inhalation Tolerance

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

Foxp3 Expressing Regulatory T-Cells in Allergic Disease

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