| First Author | Chandrasekaran P | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 8 | Pages | 2130-2140 |
| PubMed ID | 31541024 | Mgi Jnum | J:280378 |
| Mgi Id | MGI:6364669 | Doi | 10.4049/jimmunol.1900270 |
| Citation | Chandrasekaran P, et al. (2019) Regulatory Macrophages Inhibit Alternative Macrophage Activation and Attenuate Pathology Associated with Fibrosis. J Immunol 203(8):2130-2140 |
| abstractText | Diversity and plasticity are the hallmarks of macrophages. The two most well-defined macrophage subsets are the classically activated macrophages (CAMvarphis) and the IL-4-derived alternatively activated macrophages (AAMvarphis). Through a series of studies, we previously identified and characterized a distinct population of macrophages with immunoregulatory functions, collectively termed regulatory macrophages (RMvarphis). Although considerable advances have been made in understanding these various macrophage subsets, it is not known whether macrophages of one activation state can influence the other. In this study, we examined whether RMvarphis capable of inhibiting inflammatory responses of CAMvarphis could also inhibit AAMvarphis and their profibrotic responses. Our results demonstrated that RMvarphis significantly dampened the alternate activation phenotype of AAMvarphis generated in vitro and intrinsically occurring AAMvarphis from TACI(-/-) macrophages. Further, RMvarphis inhibited AAMvarphi-promoted arginase activity and fibroblast proliferation in vitro. This inhibition occurred regardless of the strength, duration, and mode of alternative activation and was only partially dependent on IL-10. In the chlorhexidine gluconate-induced peritoneal fibrosis model, AAMvarphis worsened the fibrosis, but RMvarphis rescued mice from AAMvarphi-mediated pathological conditions. Taken together, our study demonstrates that RMvarphis are a specialized subset of macrophages with a nonredundant role in limiting overt proregenerative functions of AAMvarphis, a role distinct from their well-defined role of suppression of inflammatory responses by CAMvarphis. |
