An efferocytosis-induced, IL-4-dependent macrophage-iNKT cell circuit suppresses sterile inflammation and is defective in murine CGD Academic Article Article uri icon

Overview

MeSH Major

  • Asymptomatic Diseases
  • Cerebrovascular Disorders
  • Coronary Artery Disease
  • Peripheral Arterial Disease

abstract

  • © 2013 by The American Society of Hematology Efferocytosis of apoptotic neutrophils by macrophages following tissue injury is fundamental to the resolution of inflammation and initiation of tissue repair. Using a sterile peritonitis model in mice, we identified interleukin (IL)-4–producing efferocytosing macrophages in the peritoneum that activate invariant natural killer T (iNKT) cells to produce cytokines including IL-4, IL-13, and interferon-g. Importantly, IL-4 from macrophages contributes to alternative activation of peritoneal exudate macrophages and augments type 2 cytokine production from NKTcells to suppress inflammation. The increased peritonitis in mice deficient in IL-4, NKTcells, or IL-4Ra expression on myeloid cells suggested that each is a key component for resolution of sterile inflammation. The reduced NAD phosphate oxidase is also critical for this model, because in mice with X-linked chronic granulomatous disease (X-CGD) that lack oxidase subunits, activation of iNKT cells by X-CGD peritoneal exudate macrophages was impaired during sterile peritonitis, resulting in enhanced and prolonged inflammation in these mice. Therefore, efferocytosis-induced IL-4 production and activation of IL-4–producing iNKT cells by macrophages are immunomodulatory events in an innate immune circuit required to resolve sterile inflammation and promote tissue repair.

publication date

  • April 25, 2013

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1182/blood-2012-10-461913

PubMed ID

  • 23426944

Additional Document Info

start page

  • 3473

end page

  • 3483

volume

  • 121

number

  • 17