C34-33 The Role of Dendritic Cell-specific LMAN1 in Cockroach Extract Induced Asthma

Rationale

We have previously identified LMAN1 as a receptor for house dust mite (HDM) allergens. In the airway, cell surface expression of LMAN1 was found to be highest on airway epithelial cells (AECs) and dendritic cells (DCs), suggesting that LMAN1 may have particular importance in these cell types. Recently, we reported that global loss of LMAN1 could impact HDM asthma in a sex-specific manner. Current data demonstrates that LMAN1 can also bind other mannosylated allergens including Bla g 2 (cockroach allergen), Alt a 1 (fungal allergen), and Ara h 1 (peanut allergen), implying a broader role outside of HDM recognition. This current study aims to determine the DC-specific functions of LMAN1 in allergic airway inflammation in response to cockroach allergen. Successful completion of this work will provide evidence for cell-specific targeting of LMAN1 in allergic asthma.

Methods

To study DC-specific effects of LMAN1 in vivo, Lman1fl/fl mice were crossed with CD11c-cre mice to generate Lman1fl/fl; Cd11c-Cre (DCLman1-/-). Verification of selective LMAN1 deletion was verified via PCR. Cockroach extract (CE) was used to induce asthma in DCLman1-/- mice or age- and sex-matched LMAN1fl/fl controls. Following establishment of CE-induced asthma, mice were anesthetized and lung function and airway hyperresponsiveness (AHR) were measured using a FleixVent system. Following euthanasia of animals, immune cell infiltration was measured using flow cytometry analysis of bronchoalveolar lavage (BAL) cells and lung pathology was assessed using immunohistochemistry of fixed lung tissues.

Results

Preliminary data indicate that female DCLman1-/- mice treated with CE exhibited increased airway resistance and tissue damping than LMAN1fl/fl controls, suggesting greater AHR. Interestingly, this was not accompanied with an increase in eosinophil counts in BAL, but noticeable differences in alveolar macrophage and lymphocyte counts.

Conclusion

This study suggests that in females, DC-specific LMAN1 plays a regulatory role in CE induced AHR. Molecular mechanisms underlying this cell type specific role for LMAN1 are still currently being examined. Overall, these findings support continued investigation into potential modulation of LMAN1 in a cell-type and sex-specific manner for improvement of allergic airway inflammation.

This abstract is funded by: NIH R01HL162897