Understanding macrophage functional heterogeneity in the injured liver
A transient and spatially-restricted subset of resident Kupffer Cells induced by lipid uptake.
Anna Bujko*, Federico F. De Ponti*, Zhuangzhuang Liu, Paul Collins, Tinne Thoné, Liesbet Martens, Bavo Vanneste & Charlotte L. Scott.
*These authors contributed equally
Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Belgium
In recent years the plasticity of tissue-resident macrophages (ms) has been questioned. Fitting with the idea that resident ms may not be as plastic as once thought, we have recently demonstrated that liver-resident Kupffer cells (KCs) do not display any overt activation in the context of fatty liver disease. However, this has been challenged using different models of NAFLD and whether this holds true in other inflammatory contexts has also not been assessed. To investigate this, we employed a combination of spatial proteogenomics techniques to assess hepatic m heterogeneity over time during non-alcoholic fatty liver disease (NAFLD), acetaminophen-induced liver injury (AILI) and chronic fibrosis. Consistent with previous reports, we observed a significant infiltration of monocyte-derived ms in these models, that were lost upon return to homeostasis. Further examination of the KC pool revealed the emergence of a subpopulation of resident KCs present only in the in vivo digested samples. This subset of KCs expressed a selection of genes previously associated with recruited lipid-associated macrophages (LAMs) including Trem2 and Cd36. These LAM-like KCs were uniquely positioned around damaged tissue likely explaining the difficulties in isolating these cells. Further analysis of the LAM-like KC phenotype did not reveal any increased activation in terms of pro or anti-inflammatory cytokine expression. Fitting with the LAM-like signature, we found that lipid uptake, primarily through efferocytosis is important for the generation of this phenotype. We are currently investigating the relevance of the different macrophage subsets in disease progression.
Date:
24 November 2023, 15:00 (Friday, 7th week, Michaelmas 2023)
Venue:
IMS-Tetsuya Nakamura Building, Roosevelt Dr, Headington OX3 7TY
Venue Details:
Seminar Rooms
Speaker:
Professor Charlotte Scott (VIB-UGent Center for Inflammation Research)
Organisers:
Dr Thomas Roberts (Department of Paediatrics),
Dr Rebecca Berrens (Department of Paediatrics),
Dr Filipa Simões (DPAG, IDRM, University of Oxford),
Associate Professor Carlo Rinaldi (University of Oxford, MDUK Oxford Neuromuscular Centre),
Dr Oliver Stone (University of Oxford, Department of Physiology, Anatomy and Genetics (DPAG))
Organiser contact email address:
idrmoperations-pa@idrm.ox.ac.uk
Host:
Dr Rebecca Berrens (Department of Paediatrics)
Part of:
IDRM Seminar Series
Booking required?:
Required
Booking email:
idrmoperations-pa@idrm.ox.ac.uk
Audience:
Members of the University only
Editor:
Gail Yates
