IFN-γ-producing NKT cells exacerbate sepsis by enhancing C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils

Ji Hyung Kim, Sae Jin Oh, Sehee Ahn, Doo Hyun Chung

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A role for NKT cells has been implicated in sepsis, but the mechanism by which NKT cells contribute to sepsis remains unclear. Here, we examined WT and NKT-cell-deficient mice of C57BL/6 background during cecal ligation and puncture-induced sepsis. The levels of C5a, IFN-γ, and IL-10 were higher in the serum and peritoneal fluid of WT mice than in those of CD1d-/- mice, while the mortality rate was lower in CD1d-/- mice than in WT mice. C5a blockade decreased mortality of WT mice during sepsis, whereas it did not alter that of CD1d-/- mice. As assessed by intracellular staining, NKT cells expressed IFN-γ, while neutrophils expressed IL-10. Upon coculture, IL-10-deficient NKT cells enhanced IL-10 production by WT, but not IFN-γR-deficient, neutrophils. Meanwhile, CD1d-/- mice exhibited high CD55 expression on neutrophils during sepsis, whereas those cells from WT mice expressed minimal levels of CD55. Recombinant IL-10 administration into CD1d-/- mice reduced CD55 expression on neutrophils. Furthermore, adoptive transfer of sorted WT, but not IFN-γ-deficient, NKT cells into CD1d-/- mice suppressed CD55 expression on neutrophils, but increased IL-10 and C5a levels. Taken together, IFN-γ-producing NKT cells enhance C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils, thereby exacerbating sepsis.

Original languageEnglish
Pages (from-to)2025-2035
Number of pages11
JournalEuropean Journal of Immunology
Volume44
Issue number7
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Keywords

  • C5a
  • IFN-γ
  • Neutrophils
  • NKT cell
  • Sepsis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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