Paired immunoglobulin-like receptor-B inhibits pulmonary fibrosis by suppressing profibrogenic properties of alveolar macrophages

Danielle Karo-Atar, Itay Moshkovits, Oliver Eickelberg, Melanie Königshoff, Ariel Munitz

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Macrophages are lung-resident cells that play key roles in fibrosis. Surprisingly, pathways that inhibitmacrophage functions, especially in idiopathic pulmonary fibrosis (IPF), receive little attention. The cell-surface molecule paired immunoglobulin-like receptor B (PIR-B) can suppress macrophage activation. However, its role in pulmonary fibrosis remains unknown. We sought to define the role of PIR-B in IPF. The expression of PIR-B was assessed (by quantitative PCR and flow cytometry) after bleomycin treatment. Differential cell counts, histopathology, and profibrogenic-mediator expression, for example, collagen, α-smooth muscle actin, resistin-like molecule-α (Relm-α), matrix metalloproteinase (MMP)-12, and tissue inhibitor of metalloproteinase (TIMP)-1, were determined (by ELISA quantitative PCR and flow cytometry) in the lungs of wild-type and Pirb-/- mice after bleomycin or IL-4 treatment. Bone marrow-derived wild-type and Pirb-/- macrophages were stimulated with IL-4 and assessed for Relm-α andMMP-12 expression. PIR-B was up-regulated in lung myeloid cells after bleomycin administration. Bleomycintreated Pirb2/2 mice displayed increased lung histopathology and an increased expression of collagen and of the IL-4-associated profibrogenic markers Relm-α, MMP-12, TIMP-1, and osteopontin, which were localized to alveolar macrophages. Increased profibrogenic mediator expression in Pirb-/- mice was not attributable to increased IL-4/IL-13 concentrations, suggesting that PIR-B negatively regulates IL-4-induced macrophage activation. Indeed, IL-4-treated Pirb-/- mice displayed increased Relm-α expression and Relm-α+ macrophage concentrations. IL-4-activated Pirb -/- macrophages displayed increased Relm-α and MMP-12 induction. Finally, leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3)/ immunoglobulin-like transcript-5, thehumanPIR-B orthologue, was expressed and up-regulated in lung biopsies from patients with IPF. Our results establish a key role for PIR-B in IPF, likely via the regulation of macrophage activation. Therefore, PIR-B/LILRB3 may offer a possible target for suppressing macrophage profibrogenic activity in IPF.

Original languageEnglish
Pages (from-to)456-464
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number4
StatePublished - 1 Apr 2013
Externally publishedYes


  • IL-4
  • Idiopathic pulmonary fibrosis
  • Lung
  • Macrophage
  • Paired immunoglobulin-like receptor-B

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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