LMAN1 promotes enhanced Alternaria alternata-induced airway hyperresponsiveness through alteration of alveolar macrophage and ILC2 populations

Current biologics often fail to effectively manage symptoms in severe allergic asthmatic patients, necessitating the exploration of novel therapeutic approaches. Our laboratory has recently identified LMAN1 as a novel regulatory cell surface receptor for house dust mite (HDM). Binding of LMAN1 to HDM allergens was found to depend on mannosylation, suggesting a potential broader role of this receptor in the recognition of other highly mannosylated allergens such as molds. Alternaria alternata is a ubiquitous mold often associated with severe asthma. Whether LMAN1 can also act to regulate responses to Alternaria, remains to be explored. We demonstrate that the immunodominant Alternaria allergen Alt a 1 can also bind to purified Fc-LMAN1, indicating potential involvement of this receptor. Thus, we subjected both WT and LMAN1 knockout mice to an Alternaria alternata-induced asthma model. The absence of LMAN1 resulted in a substantial increase in airway hyperresponsiveness (AHR) compared to WT animals. Interestingly, changes in AHR did not correlate with enhanced eosinophilia but, instead, went hand in hand with a reduction in alveolar macrophages and an increase in type-2 innate lymphoid cells. Work is currently ongoing to further investigate the cellular and molecular mechanisms underlying these findings. This discovery highlights LMAN1 as a promising target for innovative therapeutic interventions.