Low-density Lipoprotein Receptor-related Protein 1 Attenuates House Dust Mite-induced Eosinophilic Airway Inflammation by Suppressing Dendritic Cell-mediated Adaptive Immune Responses

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2017 Dec 24

PMID 29274414

Citations 16

Authors

Amarjit Mishra

Xianglan Yao

Ankit Saxena

Elizabeth M Gordon

Maryann Kaler

Rosemarie A Cuento

Amisha V Barochia

Pradeep K Dagur

J Philip McCoy

Karen J Keeran

Kenneth R Jeffries

Xuan Qu

Zu-Xi Yu

Stewart J Levine

Affiliations

Soon will be listed here.

Abstract

Background: Low-density lipoprotein receptor-related protein 1 (LRP-1) is a scavenger receptor that regulates adaptive immunity and inflammation. LRP-1 is not known to modulate the pathogenesis of allergic asthma.

Objective: We sought to assess whether LRP-1 expression by dendritic cells (DCs) modulates adaptive immune responses in patients with house dust mite (HDM)-induced airways disease.

Methods: LRP-1 expression on peripheral blood DCs was quantified by using flow cytometry. The role of LRP-1 in modulating HDM-induced airways disease was assessed in mice with deletion of LRP-1 in CD11c cells (Lrp1; CD11c-Cre) and by adoptive transfer of HDM-pulsed CD11b DCs from Lrp1; CD11c-Cre mice to wild-type (WT) mice.

Results: Human peripheral blood myeloid DC subsets from patients with eosinophilic asthma have lower LRP-1 expression than cells from healthy nonasthmatic subjects. Similarly, LRP-1 expression by CD11b lung DCs was significantly reduced in HDM-challenged WT mice. HDM-challenged Lrp1; CD11c-Cre mice have a phenotype of increased eosinophilic airway inflammation, allergic sensitization, T2 cytokine production, and mucous cell metaplasia. The adoptive transfer of HDM-pulsed LRP-1-deficient CD11b DCs into WT mice generated a similar phenotype of enhanced eosinophilic inflammation and allergic sensitization. Furthermore, CD11b DCs in the lungs of Lrp1; CD11c-Cre mice have an increased ability to take up HDM antigen, whereas bone marrow-derived DCs display enhanced antigen presentation capabilities.

Conclusion: This identifies a novel role for LRP-1 as a negative regulator of DC-mediated adaptive immune responses in the setting of HDM-induced eosinophilic airway inflammation. Furthermore, the reduced LRP-1 expression by circulating myeloid DCs in patients with eosinophilic asthma suggests a possible role for LRP-1 in modulating type 2-high asthma.

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