Liver-specific T regulatory type-1 cells program local neutrophils to suppress hepatic autoimmunity via CRAMP
Channakeshava Sokke Umeshappa, Patricia Solé, Bas G. J. Surewaard, Jun Yamanouchi, Saswat Mohapatra, Muhammad Myn Uddin, Robert Clarke, Mireia Ortega, Santiswarup Singha, Debajyoti Mondal, Yang Yang, Dario A.A. Vignali, Pau Serra, Paul Kubes, Pere Santamaría
Abstract
) 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.