scholarly journals CD103 integrin identifies a high IL-10-producing FoxP3+ regulatory T cell population suppressing allergic airway inflammation

2021 ◽  
Author(s):  
Sofia Tagkareli ◽  
Maria Salagianni ◽  
Ioanna Galani ◽  
Maria Manioudaki ◽  
Eleftherios Pavlos ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Airway Inflammation ◽  
Cell Population ◽  
Regulatory T Cell ◽  
Inflammatory Responses ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Treg Cells ◽  
Dependent Manner

Background: Although FoxP3+ regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. This study aimed at characterizing distinct FoxP3+ Treg subpopulations involved in the suppression of Th2-mediated allergic inflammation in the lung. Methods: We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3+ Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock-in mouse model (Foxp3creCd103dtr) enabling the specific ablation of CD103+FoxP3+ Tregs for functional studies. Results: We found that during resolution of allergic airway inflammation in mice >50% of FoxP3+ Treg cells expressed the integrin CD103 which marks FoxP3+ Treg cells of high IL-10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2-mediated inflammatory responses. CD103+FoxP3+ Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3creCd103dtr mice lead to severe alveocapillary damage and eosinophilic pneumonia, markedly reducing the lifespan of the experimental animals. Conversely, adoptive transfer of CD103+FoxP3+ Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL-10-dependent manner. Conclusion: Our study identifies a novel regulatory T cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.

scholarly journals CD103 integrin identifies a high IL-10-producing FoxP3 + regulatory T cell population suppressing allergic airway inflammation

2021 ◽  
Author(s):  
Sofia Tagkareli ◽  
Maria Salagianni ◽  
Ioanna Galani ◽  
Maria Manioudaki ◽  
Eleftherios Pavlos ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Airway Inflammation ◽  
Cell Population ◽  
Regulatory T Cell ◽  
Inflammatory Responses ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Treg Cells ◽  
Dependent Manner

Background: Although FoxP3 regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the disease context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. Objective: This study aimed at characterizing distinct FoxP3 Treg subpopulations involved in the suppression of Th2-mediated allergic inflammation in the lung. Methods: We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3 Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock-in mouse model ( Foxp3Cd103) enabling the specific ablation of CD103 FoxP3 Tregs for functional studies. Results: We found that during resolution of allergic airway inflammation in mice >50% of FoxP3 Treg cells expressed the integrin CD103 which marks FoxP3 Treg cells of high IL-10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2-mediated inflammatory responses. CD103 FoxP3 Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3Cd103 mice lead to severe alveocapillary damage, eosinophilic pneumonia, and markedly reduced lifespan of the animals. Conversely, adoptive transfer of CD103 FoxP3 Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL-10-dependent manner. Conclusion: Our study identifies a novel regulatory T cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.

scholarly journals CD103 integrin identifies a high IL‐10‐producing FoxP3 + regulatory T cell population suppressing allergic airway inflammation

Allergy ◽  
2021 ◽  
Author(s):  
Sofia Tagkareli ◽  
Maria Salagianni ◽  
Ioanna‐Evdokia Galani ◽  
Maria Manioudaki ◽  
Eleftherios Pavlos ◽  
...  
Keyword(s):  
T Cell ◽  
Airway Inflammation ◽  
Cell Population ◽  
Regulatory T Cell ◽  
Allergic Airway Inflammation

scholarly journals Androgen Receptor Signaling Augments Regulatory T Cell Functions to Attenuate Allergic Airway Inflammation

2021 ◽  
Vol 147 (2) ◽  
pp. AB3
Author(s):  
Vivek Gandhi ◽  
Jacqueline Cephus ◽  
Nowrin Chowdhury ◽  
Allison Norlander ◽  
Stokes Peebles ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
T Cell ◽  
Airway Inflammation ◽  
Regulatory T Cell ◽  
Allergic Airway Inflammation ◽  
Receptor Signaling ◽  
Androgen Receptor Signaling ◽  
Cell Functions

USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response

Life Sciences ◽  
2021 ◽  
pp. 119720
Author(s):  
Xiaoxia Hou ◽  
Fangming Zhu ◽  
Yingmeng Ni ◽  
Tiantian Chen ◽  
Juan Du ◽  
...  
Keyword(s):  
T Cell ◽  
Airway Inflammation ◽  
Regulatory T Cell ◽  
Cell Response ◽  
Allergic Airway Inflammation ◽  
T Cell Response

scholarly journals Allergen-Specific Treg Cells Upregulated by Lung-Stage S. japonicum Infection Alleviates Allergic Airway Inflammation

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhidan Li ◽  
Wei Zhang ◽  
Fang Luo ◽  
Jian Li ◽  
Wenbin Yang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Protective Effect ◽  
Airway Inflammation ◽  
Lung Tissue ◽  
Immunoglobulin E ◽  
Allergic Airway Inflammation ◽  
Treg Cells ◽  
Protective Effects ◽  
Novel Therapy ◽  
Allergen Sensitization

Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post–lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post–lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.

scholarly journals High-dose but not low-dose mainstream cigarette smoke suppresses allergic airway inflammation by inhibiting T cell function

2008 ◽  
Vol 295 (3) ◽  
pp. L412-L421 ◽  
Author(s):  
Thomas H. Thatcher ◽  
Randi P. Benson ◽  
Richard P. Phipps ◽  
Patricia J. Sime
Keyword(s):  
T Cell ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Significant Risk ◽  
Allergic Airway Inflammation ◽  
High Dose ◽  
Dependent Manner ◽  
Exposure System ◽  
Specific Antibodies ◽  
Mainstream Cigarette Smoke

Epidemiological studies have identified childhood exposure to environmental tobacco smoke as a significant risk factor for the onset and exacerbation of asthma, but studies of smoking in adults are less conclusive, and mainstream cigarette smoke (MCS) has been reported to both enhance and attenuate allergic airway inflammation in animal models. We sensitized mice to ovalbumin (OVA) and exposed them to MCS in a well-characterized exposure system. Exposure to MCS (600 mg/m3 total suspended particulates, TSP) for 1 h/day suppresses the allergic airway response, with reductions in eosinophilia, tissue inflammation, goblet cell metaplasia, IL-4 and IL-5 in bronchoalveolar lavage (BAL) fluid, and OVA-specific antibodies. Suppression is associated with a loss of antigen-specific proliferation and cytokine production by T cells. However, exposure to a lower dose of MCS (77 mg/m3 TSP) had no effect on the number of BAL eosinophils or OVA-specific antibodies. This is the first report to demonstrate, using identical smoking methodologies, that MCS inhibits immune responses in a dose-dependent manner and may explain the observation that, although smoking provokes a systemic inflammatory response, it also inhibits T cell-mediated responses involved in a number of diseases.

scholarly journals Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

2020 ◽  
Vol 8 (12) ◽  
pp. 1878
Author(s):  
Qingyu Wu ◽  
Ilka Jorde ◽  
Olivia Kershaw ◽  
Andreas Jeron ◽  
Dunja Bruder ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Influenza A Virus ◽  
Influenza A ◽  
Inflammatory Responses ◽  
Morphological Changes ◽  
Acute Infection ◽  
Allergic Airway Inflammation ◽  
Airway Hyperreactivity ◽  
Sublethal Dose

Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI. Mice infected with a sublethal dose of IAV were sensitized and challenged in an ovalbumin mediated mouse model for AAI after resolution of the acute viral infection. Histological changes, respiratory leukocytes, cytokines and airway hyperreactivity were analyzed in resolved IAV infection alone and in AAI with and without previous IAV infection. More than five weeks after infection, we detected persistent pneumonia with increased activated CD4+ and CD8+ lymphocytes as well as dendritic cells and MHCII expressing macrophages in the lung. Resolved IAV infection significantly affected subsequently induced AAI on different levels including morphological changes, respiratory leukocytes and lymphocytes as well as the pro-inflammatory cytokine responses, which was clearly diminished. We conclude that IAV has exceptional persisting effects on respiratory immunity with substantial consequences for subsequently induced AAI.

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