Liver-specific T regulatory type-1 cells program local neutrophils to suppress hepatic autoimmunity via CRAMP.
Cell Rep
; 34(13): 108919, 2021 03 30.
Article
em En
| MEDLINE
| ID: mdl-33789099
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoimunidade
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Linfócitos T Reguladores
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Catelicidinas
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Fígado
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article