The consequences of apoptosis in autoimmunity

Abstract

The clearance of apoptotic cells is a highly regulated mechanism, normally associated with antiinflammatory response. During early stages of apoptosis the cell is promptly recognized and engulfed by professional phagocytes or tissue cells to avoid the outflow of intracellular content and limit the immunological reaction against released antigens. However, increasing evidences suggest that impairment in the uptake of apoptotic cell debris is linked to the development of autoimmunity. In fact, autoantigens have been demonstrated to be content within apoptotic bodies and apoptotic cells seems to be critical in the presentation of antigens, activation of innate immunity and regulation of macrophage cytokine secretion.We herein review the known mechanisms for regulating the uptake of the products of apoptosis in the development of autoimmunity.

Apoptotic cells attenuate fulminant hepatitis by priming Kupffer cells to produce interleukin-10 through membrane-bound TGF-β

“…In addition, infusion of 1 Â 10 7 -3 Â 10 7 ACs gains the best protection against hepatitis, suggesting redundant ACs beyond the clearance ability of KCs may become necrotic in the liver. Accordingly as described, 35,36 dysfunction of AC clearance may result in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus or diabetes.…”

Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

“…Эти структуры образуются при фрагментации ядер и клеток во время апоптоза, сопровождающегося гидролизом ДНК и конденсацией хроматина и представляют собой мембранные частицы размером от 50 нм до 5000 нм [67,68]. Макрофаги, незрелые дендритные клетки [69,70] или соседние клетки [55,71] связывают и фагоцитируют как неповреждённые апоптотические клетки, так и апоптотические тельца [72]. Очевидно, что вероятность избежать поглощения и затем появиться в кровотоке у маленьких апоптотических телец больше, чем у интактных клеток.…”

Dendritic Cells in Autoimmune Diseases

“…Further, defects in the apoptosis of the immune cells and defective clearance of apoptotic cell debris due to an impaired uptake can result in development of autoimmunity. The priming of autoreactive lymphocytes by activated DCs that have taken up apoptotic materials may lead to break down of self-tolerance [34]. The role of TLRs expressed on different DC subsets has been increasingly evidenced in the pathogenesis of many autoimmune diseases [35,36].…”