Deciphering the Role of NFATc1 in Allergic Asthma: A Molecular and Immunological Perspective focusing on CD4 and CD11c Cells

Asthma is a chronic lung disease that has become a significant public health problem worldwide. Dendritic cells and T cells play a pivotal role in regulating immune responses in asthma. However, the function of NFATc1 within these cells in the context of asthma immunity remains underexplored. This study investigated NFATc1's role in CD4+ T cells and CD11c+ dendritic cells in allergic asthma utilizing a house dust mite (HDM)-induced asthma model and a human adult asthmatic cohort. In the HDM-induced asthma model, I found that Nfatc1 deletion in T cells attenuated Th2-driven eosinophilic inflammation, IgE levels, and mast cell presence in asthmatic mice. Inter-estingly, this was accompanied by an increased Th1 and Th17 response, indicating a shift to-wards a neutrophilic inflammation and suggesting Nfatc1's critical role in balancing Th2 and Th17 pathways. Additionally, an upregulation of regulatory T cells (Tregs) was observed, pointing to an adaptive mechanism aimed at controlling exacerbated inflammation. Conversely, in CD11c+ dendritic cells, Nfatc1 deficiency was associated with reduced airway hyperrespon-siveness and diminished eosinophilic inflammation, underscoring its pivotal role in dendritic cell maturation and function. This led to impaired antigen presentation and a consequent de-crease in T cell activation, highlighting the significance of Nfatc1 in dendritic cells in maintain-ing the eosinophil-dominated inflammatory response during asthma. Further aligning with these mouse model findings, translational research in humans has re-vealed significant associations between CD4+NFATc1+ and CD11c+NFATc1+ cell popula-tions and eosinophil levels in asthmatic patients, as opposed to healthy controls. This under-scores the vital role of NFATc1 in both T cells and dendritic cells in modulating Th2-mediated eosinophilic inflammation in allergic asthma. Overall, my thesis highlights NFATc1's significant role in T cells and dendritic cells, particu-larly within the context of Type 2 high allergic asthma. It reveals how NFATc1 in both cell types modulates eosinophilic inflammation and IgE-mediated allergic reactions, offering a deeper understanding of asthma pathogenesis and potential therapeutic targets for asthma treatment.