Abstract B179: The regulation of silent apoptotic cell-clearance in tissue-resident macrophages

Abstract

When normal, healthy cells die by apoptosis, they must be cleared to ensure tissue homeostasis. Failure to clear apoptotic cells (ACs) efficiently enables the release of inflammatory stimuli, such as nucleic acids, leading to tissue injury and, ultimately, autoimmunity. Clearance of ACs is largely performed by tissue-resident macrophages. Despite expressing many innate immune receptors, these cells do not respond to the potentially stimulatory ligands within ACs. Recently, the Barton Lab has identified several populations of AC-engulfing macrophages with many common features. These features include the expression of AC-recognition receptors and reduced TLR responsiveness to nucleic acids. The transcription factors KLF2 and KLF4 appear to contribute to this expression program both in vitro and in vivo in distinct AC-clearing macrophage populations. Macrophages that are removed from their environments lose this program and the program can be adopted by transferring TLR responsive macrophages into environments where endogenous silent residents are maintained. This coordinated silent immune program allows tissue-resident macrophages to maintain homeostasis while efficiently clearing ACs. Citation Format: Kathleen Pestal, Gregory M. Barton. The regulation of silent apoptotic cell-clearance in tissue-resident macrophages [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B179.