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Platelet-Sourced TGF-β Promotes Th17 Responses and Enhances Airway Neutrophilia
Ruoning Wang1, Dandan Wu1, Chunqing Wang2
1Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Abstract:
Microbial, especially fungal, sensitization has been associated with the development and exacerbation of treatment-refractory neutrophilic asthma. Among the airway-inhabiting fungi, Aspergillus fumigatus and Candida albicans are the dominant species that elicit protective T helper (Th) 17 and other T cell responses, contributing to airway neutrophilia and steroid resistance. However, it is not fully understood how fungal airway colonization impacts the immunopathogenesis of asthma. Here, we used a neutrophilic asthma model induced by C. albicans to study the immune regulation of this disease. We found that intranasal administration of C. albicans induced platelet infiltration into the lung. Platelet-expressed latent TGF-β could be activated specifically by Th17 cells and drive the commitment, maintenance, and expansion of Th17 cells. In Candida-induced asthma, an adoptive transfer of platelets enhanced Th17 responses, increasing airway neutrophil influx. Thus, managing airway mycobiota and reducing platelet intrapulmonary infiltration may serve as a promising interventional approach.
Insights
Fungal sensitization, particularly by Candida albicans, drives severe asthma by promoting T helper 17 cell responses via platelet activation. Targeting airway fungi and lung platelets may offer new asthma treatments.
Area of Science:
- Immunology
- Pulmonology
- Microbiology
Background:
- Fungal sensitization is linked to severe, treatment-resistant asthma.
- Airway fungi like Aspergillus fumigatus and Candida albicans trigger T helper 17 (Th17) cell responses, contributing to neutrophilia and steroid resistance.
Purpose of the Study:
- To investigate the immunopathogenesis of asthma influenced by fungal airway colonization.
- To elucidate the role of platelets and Th17 cells in Candida-induced neutrophilic asthma.
Main Methods:
- Induction of a neutrophilic asthma model using intranasal Candida albicans.
- Analysis of immune cell infiltration, specifically platelets, in the lungs.
- Assessment of Th17 cell activation and its interaction with platelet-derived TGF-β.
Main Results:
- Candida albicans administration led to significant platelet infiltration in the lungs.
- Platelet-expressed latent TGF-β was activated by Th17 cells, promoting Th17 cell development and expansion.
- Adoptive transfer of platelets exacerbated Th17 responses and increased airway neutrophil influx in a mouse model.
Conclusions:
- Platelets play a crucial role in amplifying Th17 responses in Candida-induced asthma.
- Managing airway fungal presence and reducing pulmonary platelet infiltration are potential therapeutic strategies for severe asthma.
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