Platelets enhance Th17 Responses and airway neutrophilia through latent TGF-β 4030

Abstract Description Microbial, especially fungal, sensitization has been associated with the development and exacerbation of treatment-refractory neutrophilic asthma. Recent research has highlighted the role of neutrophils and Th17 cells in steroid resistance. Among the airway inhabiting fungi, Aspergillus fumigatus and Candida albicans are the dominant species that elicit protective Th17 (and other T) cell responses. However, it is unclear 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. Funding Sources NIH HL148337 and AI142200. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)