Emergence of immunoregulatory Ym1+Ly6Chi monocytes during recovery phase of tissue injury

Abstract

Ly6C^hi monocytes migrate to injured sites and induce inflammation in the acute phase of tissue injury. However, once the causes of tissue injury are eliminated, monocyte-derived macrophages contribute to the resolution of inflammation and tissue repair. It remains unclear whether the emergence of these immunoregulatory macrophages is attributed to the phenotypic conversion of inflammatory monocytes in situ or to the recruitment of bone marrow-derived regulatory cells de novo. Here, we identified a subpopulation of Ly6C^hi monocytes that contribute to the resolution of inflammation and tissue repair. Ym1⁺Ly6C^hi monocytes greatly expanded in bone marrow during the recovery phase of systemic inflammation or tissue injury. Ym1⁺Ly6C^hi monocytes infiltrating into an injured site exhibited immunoregulatory and tissue-reparative phenotypes. Deletion of Ym1⁺Ly6C^hi monocytes resulted in delayed recovery from colitis. These results demonstrate that a distinct monocyte subpopulation destined to act in immunoregulation is generated in bone marrow and participates in resolution of inflammation and tissue repair.