Asthma is a chronic inflammation of the airways that affects millions of people worldwide. T lymphocytes, particularly CD4+ T cells, are one of the central regulators in the pathogenesis of asthma by orchestrating the inflammatory response within the lung tissue. Recent studies have highlighted the involvement of lipid receptors on T cells as key regulators of immune responses in asthmatic lungs, which show an altered lipid composition compared to healthy lungs. By using a chronic and acute house dust mite (HDM)-induced murine asthma model we could identify significantly different HDM-specific serum IgE levels and cytokine patterns in both, acute and chronic asthma. Our data further show that lipid receptors are crucial for the generation of T follicular helper cells, which are known as precursors of T helper 2 cells, and are in particular important for the generation of tissue-resident memory CD4⁺ T cells in the asthmatic lung. The results underline, that lipid signaling plays an essential role in the pathogenesis of asthma by regulating the immune response and contributing to airway inflammation. Elucidating the mechanism underlying lipid-receptor mediated T cell differentiation and communication with the airway epithelial barrier offers new perspectives for immunotherapeutics in asthma. Further research is mandatory to find a promising strategy for asthma treatment.