| PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production. | |
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MedLine Citation:
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PMID: 23149662 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Studies examining the role of programmed death 1 (PD-1) ligand 2 (PD-L2)/PD-1 in asthma have yielded conflicting results. To clarify its role, we examined the PD-L2 expression in biopsies from human asthmatics and the lungs of aeroallergen-treated mice. PD-L2 expression in bronchial biopsies correlated with the severity of asthma. In mice, allergen exposure increased PD-L2 expression on pulmonary myeloid dendritic cells (DCs), and PD-L2 blockade diminished allergen-induced airway hyperresponsiveness (AHR). By contrast, PD-1 blockade had no impact, suggesting that PD-L2 promotes AHR in a PD-1-independent manner. Decreased AHR was associated with enhanced serum interleukin (IL)-12 p40, and in vitro stimulation of DCs with allergen and PD-L2-Fc reduced IL-12 p70 production, suggesting that PD-L2 inhibits allergen-driven IL-12 production. In our model, IL-12 did not diminish T helper type 2 responses but rather directly antagonized IL-13-inducible gene expression, highlighting a novel role for IL-12 in regulation of IL-13 signaling. Thus, allergen-driven enhancement of PD-L2 signaling through a PD-1-independent mechanism limits IL-12 secretion, exacerbating AHR.Mucosal Immunology advance online publication 14 November 2012. doi:10.1038/mi.2012.111. |
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Authors:
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I P Lewkowich; S Lajoie; S L Stoffers; Y Suzuki; P K Richgels; K Dienger; A A Sproles; H Yagita; Q Hamid; M Wills-Karp |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-14 |
Journal Detail:
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Title: Mucosal immunology Volume: - ISSN: 1935-3456 ISO Abbreviation: Mucosal Immunol Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101299742 Medline TA: Mucosal Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Cellular and Molecular Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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