Fanning, Laura B.Buckley, Carolyn C.Xing, WeiBreslow, RebeccaKatz, Howard2013-04-262013Fanning, Laura B., Carolyn C. Buckley, Wei Xing, Rebecca G. Breslow, and Howard R. Katz. 2013. Downregulation of key early events in the mobilization of antigen-bearing dendritic cells by leukocyte immunoglobulin-like receptor b4 in a mouse model of allergic pulmonary inflammation. PLoS ONE 8(2): e57007.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10589785Leukocyte Immunoglobulin-like Receptor B4 (LILRB4) null mice have an exacerbated T helper cell type 2 (Th2) immune response and pulmonary inflammation compared with Lilrb4+/+ animals when sensitized intranasally with ovalbumin (OVA) and low-dose lipopolysaccharide (LPS) followed by challenge with OVA. Moreover, OVA-challenged Lilrb4−/− mice exhibit greater migration of antigen (Ag)-bearing dendritic cells (DCs) to lymph nodes and accumulation of interleukin 4- and interleukin 5-producing lymph node lymphocytes. The main objective of this study was to determine how the absence of LILRB4 leads to a greater number of DCs in the lymph nodes of Ag-challenged mice and increased lung Th2 inflammation. Mice were sensitized intranasally with PBS alone or containing OVA and LPS; additional cohorts were subsequently challenged with OVA. Expression of chemokine (C-C motif) ligand 21 (CCL21) in the lung was assessed immunohistologically. OVA ingestion and expression of LILRB4 and chemokine (C-C motif) receptor 7 (CCR7) were quantified by flow cytometry. Inhalation of OVA and LPS induced upregulation of LILRB4 selectively on lung Ag-bearing DCs. After sensitization and challenge, the lung lymphatic vessels of Lilrb4−/− mice expressed more CCL21, a chemokine that directs the migration of DCs from peripheral tissue to draining lymph nodes, compared with Lilrb4+/+ mice. In addition, lung DCs of challenged Lilrb4−/− mice expressed more CCR7, the CCL21 receptor. The lungs of challenged Lilrb4−/− mice also contained significantly greater numbers of CD4+ cells expressing interleukin-4 or interleukin-5, consistent with the greater number of Ag-bearing DCs and Th2 cells in lymph nodes and the attendant exacerbated Th2 lung pathology. Our data establish a new mechanism by which LILRB4 can downregulate the development of pathologic allergic inflammation: reduced upregulation of key molecules needed for DC migration leading to decreases in Th2 cells in lymph nodes and their target tissue.en-USBiologyDevelopmental BiologyMorphogenesisCell MigrationImmunologyImmunityImmunoregulationInflammationImmunologic SubspecialtiesPulmonary ImmunologyAllergy and HypersensitivityImmunomodulationImmunopathologyModel OrganismsAnimal ModelsMouseJournal Article2013-04-2610.1371/journal.pone.0057007