The Silent Undertakers: Macrophages Programmed for Efferocytosis Judith E. Allen, Dominik Rückerl  Immunity  Volume 47, Issue 5, Pages 810-812 (November 2017) DOI: 10.1016/j.immuni.2017.10.010 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Tissue Macrophages Are Programmed to Silently Remove Apoptotic Cells A specialized macrophage population in the T cell zone of skin-draining lymph nodes (left coffin) contributes to efferocytosis of the vast numbers of cells undergoing apoptosis during the contraction phase of an immune response as well as under steady-state conditions. These long-lived, tissue-resident macrophages are characterized by the expression of CX3CR1, CD11c, and TAM family members but do not seem to be involved in antigen priming or tolerization of T cells and are distinct both functionally and developmentally from DCs. In the serous cavities and possibly other tissues, resident macrophages (right coffin) are silenced by local tissue signals to avoid inflammatory activation to endogenous nucleic acids contained in apoptotic cells. Tissue environmental factors induce the transcription factors KLF2 and KLF4, which enhance expression of apoptotic-cell receptors (e.g., Tim4, Marco) as well as negative regulators (e.g., SOCS3, DUSP1, and Ptpn6) of TLR7 and TLR9 signaling, raising the threshold of activation and preventing the production of inflammatory cytokines in response to apoptotic cells. Immunity 2017 47, 810-812DOI: (10.1016/j.immuni.2017.10.010) Copyright © 2017 Elsevier Inc. Terms and Conditions