| First Author | Umeshappa CS | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 13 | Pages | 108919 |
| PubMed ID | 33789099 | Mgi Jnum | J:304313 |
| Mgi Id | MGI:6694777 | Doi | 10.1016/j.celrep.2021.108919 |
| Citation | Umeshappa CS, et al. (2021) Liver-specific T regulatory type-1 cells program local neutrophils to suppress hepatic autoimmunity via CRAMP. Cell Rep 34(13):108919 |
| abstractText | Neutrophils with immunoregulatory properties, also referred to as type-2 neutrophils (N2), myeloid-derived suppressor cells (MDSCs), or tumor-associated neutrophils (TANs), comprise a heterogeneous subset of cells that arise from unknown precursors in response to poorly understood cues. Here, we find that, in several models of liver autoimmunity, pharmacologically induced, autoantigen-specific T regulatory type-1 (TR1) cells and TR1-cell-induced B regulatory (Breg) cells use five immunoregulatory cytokines to coordinately recruit neutrophils into the liver and program their transcriptome to generate regulatory neutrophils. The liver-associated neutrophils from the treated mice, unlike their circulating counterparts or the liver neutrophils of sick mice lacking antigen-specific TR1 cells, are proliferative, can transfer disease protection to immunocompromised hosts engrafted with pathogenic effectors, and blunt antigen-presentation and local autoimmune responses via cathelin-related anti-microbial peptide (CRAMP), a cathelicidin, in a CRAMP-receptor-dependent manner. These results, thus, identify antigen-specific regulatory T cells as drivers of tissue-restricted regulatory neutrophil formation and CRAMP as an effector of regulatory neutrophil-mediated immunoregulation. |
