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JCI Insight. 2017 Nov 2;2(21). pii: 94929. doi: 10.1172/jci.insight.94929.

Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen.

Author information

1
Department of Medicine, Division of Pulmonary and Critical Care.
2
Department of Comparative Medicine.
3
Department of Chemistry, and.
4
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
5
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
6
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.

Abstract

Phospholipase A2 (PLA2) enzymes regulate the formation of eicosanoids and lysophospholipids that contribute to allergic airway inflammation. Secreted PLA2 group X (sPLA2-X) was recently found to be increased in the airways of asthmatics and is highly expressed in airway epithelial cells and macrophages. In the current study, we show that allergen exposure increases sPLA2-X in humans and in mice, and that global deletion of Pla2g10 results in a marked reduction in airway hyperresponsiveness (AHR), eosinophil and T cell trafficking to the airways, airway occlusion, generation of type-2 cytokines by antigen-stimulated leukocytes, and antigen-specific immunoglobulins. Further, we found that Pla2g10-/- mice had reduced IL-33 levels in BALF, fewer type-2 innate lymphoid cells (ILC2s) in the lung, less IL-33-induced IL-13 expression in mast cells, and a marked reduction in both the number of newly recruited macrophages and the M2 polarization of these macrophages in the lung. These results indicate that sPLA2-X serves as a central regulator of both innate and adaptive immune response to proteolytic allergen.

PMID:
29093264
PMCID:
PMC5752296
DOI:
10.1172/jci.insight.94929
[Indexed for MEDLINE]
Free PMC Article

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