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Eosinophil-derived IL-4 is necessary to establish the inflammatory structure in innate inflammation.

Anja KolbingerTim J SchäufeleHanna SteigerwaldJoschua FriedelSandra PierreGerd GeisslingerKlaus Scholich
Published in: EMBO molecular medicine (2022)
Pathogen-induced inflammation comprises pro- and anti-inflammatory processes, which ensure pathogen removal and containment of the proinflammatory activities. Here, we aimed to identify the development of inflammatory microenvironments and their maintenance throughout the course of a toll-like receptor 2-mediated paw inflammation. Within 24 h after pathogen-injection, the immune cells were organized in three zones, which comprised a pathogen-containing "core-region", a bordering proinflammatory (PI)-region and an outer anti-inflammatory (AI)-region. Eosinophils were present in all three inflammatory regions and adapted their cytokine profile according to their localization. Eosinophil depletion reduced IL-4 levels and increased edema formation as well as mechanical and thermal hypersensitivities during resolution of inflammation. Also, in the absence of eosinophils PI- and AI-regions could not be determined anymore, neutrophil numbers increased, and efferocytosis as well as M2-macrophage polarization were reduced. IL-4 administration restored in eosinophil-depleted mice PI- and AI-regions, normalized neutrophil numbers, efferocytosis, M2-macrophage polarization as well as resolution of zymosan-induced hypersensitivity. In conclusion, IL-4-expressing eosinophils support the resolution of inflammation by enabling the development of an anti-inflammatory framework, which encloses proinflammatory regions.
Keyphrases
  • oxidative stress
  • anti inflammatory
  • toll like receptor
  • diabetic rats
  • immune response
  • artificial intelligence
  • candida albicans
  • high glucose
  • single molecule
  • drug induced
  • type diabetes
  • adipose tissue