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Published on: April 29, 2015
Early-Derived Murine Macrophages Temporarily Renounce Tissue Identity during Acute Systemic Inflammation
Radika Soysa1, Jonathan C Bean2, Xia Wu3
1Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA; and radika.soysa@gmail.com.
Abstract:
In mice, a subset of cardiac macrophages and Kupffer cells derive from fetal precursors, seed the developing tissues, self-renew locally, and persist into adulthood. In this study we investigated how these cells survive acute systemic inflammation. In both tissues, early-derived subsets rapidly responded to acute systemic inflammation by assuming a temporary nonclassical activation state featuring upregulation of both proinflammatory (Il1b, Tnf, Nfkb1), and anti-inflammatory (Il10, Il4ra, Nfkbiz) genes. During this process, transcription factor genes associated with myeloid identity (Spi1, Zeb2) were upregulated, whereas those associated with tissue specificity (Nr1h3 for Kupffer cells and Nfatc2 and Irf4 for cardiac macrophages) were downregulated, suggesting that the cells reasserted their myeloid identity but renounced their tissue identity. Most of these changes in gene expression reverted to steady-state levels postresolution. We conclude that these early-derived macrophage subsets are resilient in the face of acute stress by temporary loss of adaptation to local tissue-specific niches while reasserting their generic myeloid identity.
Insights
Fetal-derived cardiac macrophages and Kupffer cells survive inflammation by temporarily losing tissue identity and reasserting myeloid identity. These early-derived immune cells regain their specialized functions after the inflammatory stress resolves.
Area of Science:
- Immunology
- Cell Biology
- Tissue-specific macrophages
Background:
- A subset of cardiac macrophages and Kupffer cells originate from fetal precursors.
- These cells self-renew and persist in tissues into adulthood.
- Their survival mechanisms during acute systemic inflammation are not fully understood.
Purpose of the Study:
- To investigate how early-derived cardiac macrophages and Kupffer cells survive acute systemic inflammation.
- To understand the changes in gene expression and cellular identity during inflammatory stress.
Main Methods:
- Analysis of gene expression in cardiac macrophages and Kupffer cells from mice subjected to acute systemic inflammation.
- Focus on transcription factor gene changes related to myeloid and tissue-specific identity.
Main Results:
- Early-derived macrophages transiently adopted a nonclassical activation state, upregulating both pro- and anti-inflammatory genes.
- Genes associated with myeloid identity (Spi1, Zeb2) were upregulated.
- Genes linked to tissue specificity (Nr1h3, Nfatc2, Irf4) were downregulated, indicating a loss of tissue adaptation.
- Gene expression largely reverted to baseline after inflammation resolution.
Conclusions:
- Early-derived cardiac macrophages and Kupffer cells demonstrate resilience to acute inflammation.
- This resilience is achieved through a temporary loss of tissue-specific adaptation and reassertion of generic myeloid identity.
- These cells can recover their specialized functions post-inflammation.
