| First Author | Jiao S | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 6416 |
| PubMed ID | 37828059 | Mgi Jnum | J:341625 |
| Mgi Id | MGI:7542348 | Doi | 10.1038/s41467-023-42187-5 |
| Citation | Jiao S, et al. (2023) SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness. Nat Commun 14(1):6416 |
| abstractText | Alteration of the size and stiffness of the nucleus triggered by environmental cues are thought to be important for eukaryotic cell fate and function. However, it remains unclear how context-dependent nuclear remodeling occurs and reprograms gene expression. Here we identify the nuclear envelope proteins SUN1/2 as mechano-regulators of the nucleus during M1 polarization of the macrophage. Specifically, we show that LPS treatment decreases the protein levels of SUN1/2 in a CK2-betaTrCP-dependent manner to shrink and soften the nucleus, therefore altering the chromatin accessibility for M1-associated gene expression. Notably, the transmembrane helix of SUN1/2 is solely required and sufficient for the nuclear mechano-remodeling. Consistently, SUN1/2 depletion in macrophages facilitates their phagocytosis, tissue infiltration, and proinflammatory cytokine production, thereby boosting the antitumor immunity in mice. Thus, our study demonstrates that, in response to inflammatory cues, SUN1/2 proteins act as mechano-regulators to remodel the nucleus and chromatin for M1 polarization of the macrophage. |
