Paired immonoglobulin-like receptor-B critically regulates Th2-response in experimental asthma

Dana Shik, Ariel Munitz.

Author address: 

Tel Aviv University, Microbiology and Human Immunology, Tel Aviv, Ramat Aviv, IL

Abstract: 

Background: Paired-Immunoglobulin-like receptor B (PIR-B) is an immunoreceptor tyrosine-based inhibitory motif-containing receptor expressed predominantly by myeloid cells, which counter-regulates their function. Recent data report exaggerated Th2 activation in response to Alum/OVA sensitization in Pirb-/- mice due to impaired dendritic cell function. Yet, the role of PIR-B in experimental asthma, a "œhallmark" Th2-disease, is unknown. Objective: To define the role of PIR-B in experimental asthma. Methods: Wild type (WT) and Pirb-/- mice were intranasally-challenged with Aspergillus fumigatus (Af) extract (12mg/60ml/mouse, 6 challenges/2 weeks). PIR-B expression in the lungs of WT mice was assessed using flow cytometry combining various myeloid cell markers. BALF was assessed for total and differential cell counts as well as cytokine (IFN-g, IL-13, IL-4, IL-5) and chemokine profiles (CCL17, CCL22, CXCL9, CXCL10) (ELISA, qPCR). Results: Expression of PIR-B mRNA was upregulated in the lungs of WT mice following Af-challenge. Af-challenged WT mice displayed significant infiltration of multiple PIR-B+ cells including eosinophils, neutrophils, macrophages and various myeloid cell subsets. Unexpectedly, allergen-challenged Pirb-/- mice displayed significantly increased lung lymphocyte and neutrophil accumulation compared with WT mice. Pirb-/- mice exhibited decreased levels of IL-4 and IL-13, CCL17 and CCL22 compared with WT mice. Conversely, Pirb-/- mice demonstrated significantly increased IFNg and IFNg-dependent chemokines, CXCL9 and CXCL10, compared with WT mice. Conclusions: These results demonstrate a crucial and unexpected role for PIR-B governing Th2-responses in experimental asthma.
2011

abstract No: 

OP4

Full conference title: 

European Respiratory Congress
    • ERS 21st (2011)