PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production.
Mucosal Immunol
; 6(4): 728-39, 2013 Jul.
Article
in En
| MEDLINE
| ID: mdl-23149662
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asthma
/
Dendritic Cells
/
Interleukin-12
/
Programmed Cell Death 1 Ligand 2 Protein
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mucosal Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2013
Document type:
Article
Affiliation country:
Estados Unidos