LMAN1 is a receptor for house dust mite allergens

• Published in: Cell reports (Cambridge) 2023-03, Vol.42 (3), p.112208-112208, Article 112208
• Main Authors: Miller, Madelyn H., Swaby, Lindsay G., Vailoces, Vanessa S., LaFratta, Maggie, Zhang, Yuan, Zhu, Xiang, Hitchcock, Dorilyn J., Jewett, Travis J., Zhang, Bin, Tigno-Aranjuez, Justine T.
• Format: Article
• Language: English
• Subjects: allergen receptors; Allergens; Animals; Asthma; CP: Immunology; Cytokines - metabolism; ERGIC-53; house dust mite; Humans; Hypersensitivity; LMAN1; Pyroglyphidae
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112208

Development of therapies with the potential to change the allergic asthmatic disease course will require the discovery of targets that play a central role during the initiation of an allergic response, such as those involved in the process of allergen recognition. We use a receptor glycocapture technique to screen for house dust mite (HDM) receptors and identify LMAN1 as a candidate. We verify the ability of LMAN1 to directly bind HDM allergens and demonstrate that LMAN1 is expressed on the surface of dendritic cells (DCs) and airway epithelial cells (AECs) in vivo. Overexpression of LMAN1 downregulates NF-κB signaling in response to inflammatory cytokines or HDM. HDM promotes binding of LMAN1 to the FcRγ and recruitment of SHP1. Last, peripheral DCs of asthmatic individuals show a significant reduction in the expression of LMAN1 compared with healthy controls. These findings have potential implications for the development of therapeutic interventions for atopic disease. [Display omitted] •Receptor glycocapture screen identifies LMAN1 as an HDM receptor•Binding of LMAN1 to HDM allergens requires LMAN1 CRD•LMAN1 downregulates NF-κB signaling through binding FcRγ and recruitment of SHP1•Asthmatic individuals show reduced cell surface expression of LMAN1 on peripheral DCs Miller et al. describe the identification of LMAN1 as a receptor for HDM using an unbiased receptor glycocapture screen. Engagement of LMAN1 by HDM restrains inflammatory responses. Such regulatory mechanisms may be disrupted in asthmatic individuals who show reduced expression of LMAN1 on DCs.