Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton’s tyrosine kinase-dependent pathway

Abstract

Initiation of the innate sterile inflammatory response that can develop in response to microparticle (MP) exposure is little understood. A potent type 2 immune response associated with accumulation of neutrophils, eosinophils, and alternatively activated (M2) macrophages was observed in response to sterile MPs similar in size to wear debris associated with prosthetic implants. Although elevations in IL-33 and type 2 cytokines occurred independently of Caspase-1 inflammasome signaling, the response was dependent on Bruton’s tyrosine kinase (BTK). IL-33 was produced by macrophages and BTK-dependent expression of IL-33 by macrophages was sufficient to initiate the type 2 response. Analysis of inflammation in patient periprosthetic tissue also revealed type 2 responses under aseptic conditions in patients undergoing revision surgery. These findings indicate for the that MP-induced sterile inflammation is initiated by macrophages activated to produce IL-33. They further suggest that both BTK and IL-33 may provide therapeutic targets for wear debris induced periprosthetic inflammation.

Lysophosphatidic Acid Regulates the Differentiation of Th2 Cells and Its Antagonist Suppresses Allergic Airway Inflammation

“…Therefore, we focused attention on macrophages because IL-33 derived from macrophages induced IL-13 production by ILC2 and increased airway hypersensitivity in influenza-infected mice [34]. Several studies have reported that macrophages produce IL-33 [35, 36]. In the present findings, since the number of macrophages correlated with IL-33 in the lungs, it is likely that LPA may elicit macrophage-derived IL-33 production, leading to an increase in IL-13 production in the lungs in our mouse model of allergic inflammation.…”

The effect of geniposide on chronic unpredictable mild stress‐induced depressive mice through BTK/TLR4/NF‐κB and BDNF/TrkB signaling pathways

“…BTK modulates toll‐like receptors, including TLR2, TLR4, and TLR9, to regulate the secretion of inflammatory cytokines (Mishra et al, 2019). TLRs are connected with plentiful cytoplasmic adaptor proteins, including myeloid differentiation factor 88 (MyD88) (Rip et al, 2019).…”

Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling on intestinal epithelial cells

“…To assess whether type 2 responses were generally refractory to deletion of A2BARs on macrophages, effects on a previously established peritoneal type 2 immune response to sterile inert microparticles (MPs) [23] were examined. Mice were inoculated in the peritoneal cavity with MPs, triggering myeloid cell infiltration and potent elevations in type 2 cytokines, as previously described [23]. As shown in supplementary Fig.1, at 48 hrs after inoculation pronounced elevations in type 2 cytokines and increases in M2 macrophages were blocked in MP-inoculated LysM Cre -A2BAR fl/fl mice compared to inoculated LysM Cre mice in this experimental model of sterile inflammation.…”