Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn’s Disease. Previously, we and others found that TNF blocks the emergence and function of alternative-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balance of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages, we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis, and signaling pathway deconvolution. We found that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way, dependent on JNK signaling via the type 1 TNF receptor on specific populations of alternative-activated macrophages. We further determined that JNK signaling has a profound and broad effect on activated macrophage gene expression. Our findings suggest that TNF’s anti-M2 effects evolved to specifically modulate components of tissue and reparative M2 macrophages and TNF is therefore a context-specific modulator of M2 macrophages rather than a panM2 inhibitor.
Details
Original language | English |
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Article number | e202101315 |
Journal | Life science alliance |
Volume | 5 |
Issue number | 4 |
Publication status | Published - 13 Jan 2022 |
Peer-reviewed | Yes |
External IDs
unpaywall | 10.26508/lsa.202101315 |
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Scopus | 85124156566 |
PubMed | 35027468 |
Mendeley | 40d4ce05-12a7-308c-a465-a6b295fa9217 |
WOS | 000744116400001 |
ORCID | /0000-0001-9599-8632/work/142241723 |