LMAN1, a Negative Regulator of the Response to House Dust Mite

Abstract

Abstract We have utilized an unbiased receptor capture approach (CaptiRec) to screen for receptors on dendritic cells which directly bind HDM. Using this technique, we have identified LMAN1 (Lectin, Mannose Binding 1) as a candidate receptor for HDM. LMAN1 is a mannose binding lectin which is primarily known to act as a cargo transporter between the ER, ERGIC, and Golgi compartments. The role played by LMAN1 in the recognition of and response to HDM, is currently unknown. We verify the ability of LMAN1 to directly bind HDM proteins biochemically and in a cellular context. Furthermore, we present evidence to demonstrate that LMAN1 downregulates NF-κB responses in response to inflammatory cytokines and to HDM. Loss of LMAN1 on DCs used for allergic sensitization leads to exacerbated airway inflammation in a HDM model of allergic asthma. Lastly, peripheral DCs of asthmatics show a significant reduction in expression of LMAN1 compared to healthy controls. These findings have potential implications for the development of novel therapeutic interventions for allergy and allergic asthma. Supported by American Lung Association Innovation Award IA-695632