Toll-like receptor 3 expression in myeloid cells is essential for efficient regeneration after acute pancreatitis in mice
| Autor: | Lina M. Staufer, Katja Steiger, Bernhard Holzmann, Felicitas Altmayr, Daniel Hartmann, Leonie S. Jochheim, Ludwig A Kuebelsbeck, Norbert Hüser, Roland M. Schmid, Guido von Figura, Ana Hidalgo-Sastre, Widya Johannes, Monica Ronderos |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death Myeloid viruses Immunology Cell Gene Expression chemical and pharmacologic phenomena Inflammation Biology 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Macrophage Animals Regeneration Myeloid Cells Receptor Cell Proliferation Mice Knockout Toll-like receptor Regeneration (biology) Macrophages virus diseases hemic and immune systems Immunohistochemistry ddc Toll-Like Receptor 3 Disease Models Animal 030104 developmental biology medicine.anatomical_structure Pancreatitis Acute Disease Cancer research Cytokines medicine.symptom Biomarkers 030215 immunology Signal Transduction |
| Zdroj: | European journal of immunologyReferences. 51(5) |
| ISSN: | 1521-4141 |
| Popis: | Stringent regulation of the inflammatory response is crucial for normal tissue regeneration. Here, we analyzed the role of Toll-like receptor 3 (TLR3) in pancreatic regeneration after acute pancreatitis (AP). AP was induced by caerulein treatment in mice with global TLR3 deficiency (TLR3OFF ) or in mice re-expressing TLR3 exclusively in the myeloid cell lineage (TLR3Mye ). Compared to WT mice, TLR3OFF mice had a markedly increased formation of acinar-to-ductal metaplasia (ADM) that persisted until day 7 after initiation of AP. Pancreatic tissue of WT mice was completely regenerated after 5 days with no detectable ADM structures. The enhancing effect of TLR3-deficiency on ADM formation was closely linked with an increased and prolonged accumulation of macrophages in pancreata of TLR3OFF mice. Importantly, the phenotype of TLR3OFF mice was rescued in TLR3Mye mice, demonstrating the causative role of myeloid cell selective TLR3 signaling. Moreover, in vitro stimulation of macrophages through TLR3 initiated cell death by a caspase-8-associated mechanism. Therefore, these findings provide evidence that TLR3 signaling in myeloid cells is sufficient to limit inflammation and ADM formation and to promote regeneration after AP. Notably, resolution of inflammation after AP was associated with macrophage sensitivity to TLR3-mediated cell death. |
| Databáze: | OpenAIRE |
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