Skip to Content
MilliporeSigma
  • Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF.

Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF.

Life science alliance (2022-01-15)
Stefanie Dichtl, David E Sanin, Carolin K Koss, Sebastian Willenborg, Andreas Petzold, Maria C Tanzer, Andreas Dahl, Agnieszka M Kabat, Laura Lindenthal, Leonie Zeitler, Sabrina Satzinger, Alexander Strasser, Matthias Mann, Axel Roers, Sabine A Eming, Karim C El Kasmi, Edward J Pearce, Peter J Murray
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 pan-M2 inhibitor.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, ≥96% (agarose gel electrophoresis)
Sigma-Aldrich
JNK-IN-8, ≥96% (HPLC)