Eosinophil‐derived IL‐4 is necessary to establish the inflammatory structure in innate inflammation. Issue 2 (21st December 2022)

• Record Type: Journal Article
• Authors: Kolbinger, Anja; Schäufele, Tim J; Steigerwald, Hanna; Friedel, Joschua; Pierre, Sandra; Geisslinger, Gerd; Scholich, Klaus
• Is Part Of: EMBO molecular medicine. Volume 15:Issue 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-21
• Subjects: eosinophil -- innate inflammation -- interleukin‐4 -- macrophages -- microenvironments; Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.202216796
• Languages: English
• ISSNs: 1757-4676

Abstract

Abstract: 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. Synopsis: Multiplex immunohistochemistry identified a regional architecture in TLR‐type 2 inflammation, which comprised the pathogen‐containing core region, a surrounding pro‐inflammatory region, and an outer anti‐inflammatory region. Once established, the regions were stable throughout the course of inflammation. Eosinophils were found in all three regions and adapted their cytokine profile to their specific microenvironments. Depletion of eosinophils destroyed the regional structure outside of the core region. Depletion of eosinophils increased neutrophil recruitment, edema formation and thermal hypersensitivity. IL‐4 application rescued the regional structure and allowed a normal immune response in eosinophil‐depleted mice. Abstract : Multiplex immunohistochemistry identified a regional architecture in TLR‐type 2 inflammation, which comprised the pathogen‐containing core region, a surrounding pro‐inflammatory region, and an outer anti‐inflammatory region. Once established, the regions were stable throughout the course of inflammation.