| First Author | Dichtl S | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 4 | PubMed ID | 35027468 |
| Mgi Jnum | J:319551 | Mgi Id | MGI:6861319 |
| Doi | 10.26508/lsa.202101315 | Citation | Dichtl S, et al. (2022) Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF. Life Sci Alliance 5(4) |
| abstractText | 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. |
