Phagocytosis of Apoptotic Cells and Immune Regulation

Abstract

The termination of the apoptotic programme occurs in most cases via recognition and clearance by phagocytes, especially the professional phagocytes, such as macrophages and immature dendritic cells. Engulfed cells do not simply disappear from the midst of living tissues. The fine-defined presentation of yielded self-antigens to T cells is a central event in the induction or the maintenance of the peripheral immune tolerance to self. Conversely, abnormality in this pathway may contribute to the pathogenesis of systemic and organ-specific autoimmune diseases. We herein reviewed the relationship between phagocytosis of apoptotic cells and immune regulation, especially the effects of engulfed apoptotic cells on immune tolerance and autoimmune diseases.

N-(4-iodophenyl)-N′-(2-chloroethyl)urea as a microtubule disrupter: in vitro and in vivo profiling of antitumoral activity on CT-26 murine colon carcinoma cell line cultured and grafted to mice

“…That phenomenon is not unique, as it has been already reported for other antimicrotubule agents by Schimming et al (1999). We hypothesise that cells with alkylated b-tubulin might be eliminated quickly in vivo via phagocytosis and/or ubiquitin proteasome degradation pathways, as described previously (Krysko et al, 2006;Liu et al, 2006;Wang et al, 2006). Likewise, the tumoricidal concentration of ICEU necessary to kill cells should be higher as compared to in vitro when one considers the interrelated influence of physiological parameters such as perfusion, necrosis, cell density and interstitial pressure that may affect the diffusion of the drug into the tumoral tissues and the neoplastic cells.…”

Type I IFNs Control Antigen Retention and Survival of CD8α+ Dendritic Cells after Uptake of Tumor Apoptotic Cells Leading to Cross-Priming

“…Hence, clearance of apoptotic cells by phagocytes results in anti-inflammatory and immunosuppressive effects, thus hampering the onset of T cell effector responses. This occurs because engulfment of apoptotic material results in lack of induction of proinflammatory cytokines or even in the release of immunoregulatory factors that maintain DC in an immature state (25). The findings reported in this study demonstrate that IFN-I can act as a powerful switch signal for DC promoting cross-priming in vivo against a largely tolerogenic type of Ag, such as Ag derived from tumor apoptotic cells.…”

How apoptosis got the immune system in shape

“…This trend likely indicates that the execution phase of apoptosis, which has been intensively studied, is most relevant to understand the etiology of AIDS and cancer, while the last step of apoptosis, the removal of the dying cells, which is currently being highly studied, is more relevant to the development of autoimmune diseases. It is being recognized that apoptosing cells are sending eat-me and danger signals into their environment and, most importantly, that once taken up by macrophages or immature dendritic cells they can influence the immune system in multiple ways [97]. In this regard, presentation of self antigens derived from apoptotic cells toT cells is likely important for maintaining peripheral tolerance.…”