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

Ref ID: 18429

Author:

Dana Shik, Ariel Munitz.

Author address:

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

Full conference title:

European Respiratory Congress

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.

Abstract Number: OP4

Conference Year: 2011

Link to conference website: http://www.ers-education.org/ersMade/abstract_print_11/files/Abstract_book_2011.pdf

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