The Role of Efferocytosis in Autoimmune Diseases

Abstract

Apoptosis happens continuously for millions of cells along with the active removal of apoptotic debris in order to maintain tissue homeostasis. In this respect, efferocytosis, i.e., the process of dead cell clearance, is orchestrated through cell exposure of a set of “find me,” “eat me,” and “tolerate me” signals facilitating the engulfment of dying cells through phagocytosis by macrophages and dendritic cells. The clearance of dead cells via phagocytes is of utmost importance to maintain the immune system tolerance to self-antigens. Accordingly, this biological activity prevents the release of autoantigens by dead cells, thus potentially suppressing the undesirable autoreactivity of immune cells and the appearance of inflammatory autoimmune disorders as systemic lupus erythematous and rheumatoid arthritis. In the present study, the apoptosis pathways and their immune regulation were reviewed. Moreover, efferocytosis process and its impairment in association with some autoimmune diseases were discussed.

Efferocytosis capacities of blood monocyte‐derived macrophages in systemic sclerosis

“…These three connective tissue disorders are characterized by a common expression of autoantibodies targeting intranuclear components (ANA such as anti‐ribonucleoprotein and anti‐DNA antibodies in SLE, anti‐SSA or SSB in SLE or Sjögren syndrome, and anti‐centromere proteins, anti‐topoisomerase I or anti‐RNA‐polymerase III antibodies in SSc). The hypothesis of an increase in autoantigens leading to an excess of autoantibodies has been proposed to explain these ANA, especially in SLE . Interestingly, apoptotic cells express at their membrane surface antigens that are normally expressed in the nucleus .…”

“…The clearance of apoptotic cells is a process called efferocytosis . Macrophages (MΦ) are one of the key immune cells performing efferocytosis in vivo and are essential to limit autoimmunity and inflammation . Hence, a deficiency of macrophagic efferocytosis has been found in several systemic autoimmune diseases, characterized by positive ANA, such as systemic lupus erythematosus (SLE) and Sjögren syndrome .…”

Efferocytosis: molecular mechanisms and pathophysiological perspectives

“…An evolutionary conserved process called programmed cell removal or efferocytosis accurately and quickly eliminates apoptotic cells from the body. Any disturbance in efferocytosis can lead to various diseases such as inflammatory and autoimmune diseases, atherosclerosis and cancer . The proper understanding of the mechanism of efferocytosis can create new insights in the treatment of these diseases.…”

“…Autoimmune disorders occur because of the impairment of immune system tolerance to autoantigens. Disturbances of the efferocytosis process, as the result of an impaired clearance of apoptotic cells because of abnormal find‐me or eat‐me signals, defects in surface receptors of phagocytes, bridging molecules or their signaling pathways, may result in autoimmune disorders in humans, including systemic lupus erythematosus and rheumatoid arthritis …”

“…Any disturbance in efferocytosis can lead to various diseases such as inflammatory and autoimmune diseases, atherosclerosis and cancer. 3,4 The proper understanding of the mechanism of efferocytosis can create new insights in the treatment of these diseases.…”