PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)728-739
Number of pages12
JournalMucosal Immunology
Volume6
Issue number4
DOIs
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lewkowich, I. P., Lajoie, S., Stoffers, S. L., Suzuki, Y., Richgels, P. K., Dienger, K., Sproles, A. A., Yagita, H., Hamid, Q., & Wills-Karp, M. (2013). PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production. Mucosal Immunology, 6(4), 728-739. https://doi.org/10.1038/mi.2012.111