Evaluation of the IL-22/IL-22 binding protein axis in macrophage phagocytosis during acute lung injury 4247
Year: 2025
Type: article
Abstract: Description Interleukin 22 binding protein (IL-22BP) is a monomeric protein that is produced by myeloid and epithelial cells. The only documented function of this protein is to inhibit the cytokine IL-22. Our published work has demonstrated that IL-22BP knockout (IL22BPKO) have significantly exacerbated inflammation and macrophage influx compared to wild type controls in a bleomycin model of injury. We hypothesized that macrophages are critical to the exuberant inflammation observed in IL22BPKO mice and we tested this by administering clodronate. Surprisingly, IL22BKO mice underwent limited macrophage ablation after treatment suggesting a phagocytosis defect. In-vitro studies support this concept, as primary macrophages from IL22BPKO mice have limited uptake of IgG or phosphatidyl serine coated beads. Importantly, IL-22 treatment did not enhance phagocytosis. We postulate that the IL22BP associated defect is in part due to a reduction in scavenger and lipid recognition receptors as IL-22BPKO mice had reduced expression of macrophage scavenger receptor 1, scavenger receptor 1, lectin type oxidized LDL receptor and transcription factor peroxisome proliferator-activated receptor gamma. Further, lipid profiling revealed selective lipid metabolism in IL-22BPKO mice. These data suggest lipid uptake is compromised in IL-22BPKO-derived macrophages and demonstrates that IL-22BP may have a novel role in lipid recognition and macrophage function. Funding Sources n/a Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)
Source: The Journal of Immunology
Authors: Mazvita Banele Chakawa, Zhe Zhang, Michaela Allen, Derek Pociask
Institution: Tulane University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416448218
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