Abstract: Autophagy is a highly conserved process in all eukaryotic organisms that has been adapted for a multitude of divergent functions. The mammalian immune system is no exception, with various hematopoietic cells utilizing this intracellular remodeling process for immune homeostasis.
In this chapter, we will focus on the role of autophagy in three major areas of immune function: homeostasis of lymphocytes, antigen presentation and pathogen clearance, and thymic selection for immune tolerance.
First, autophagy has been shown to be crucial and indispensible for the survival and intracellular homeostasis of both T and B lymphocytes in vivo.
This has been demonstrated using multiple genetic models of autophagy ablation as well as pharmacological inhibition of various autophagic signaling pathways. Second, autophagy has been shown to enhance antigen presentation in several types of leukocytes of the innate immune system, including macrophages and dendritic cells, and to both promote and inhibit the clearance of several intracellular pathogens.
Lastly, in a very nascent field of autophagy in thymic epithelial cells, autophagy promotes the processing and surface display of many endogenous antigens in order to influence negative selection and tolerance of developing thymocytes. These examples will clearly demonstrate the complex applications that the panoply of immune cells has evolved to initiate and maintain immune function using an archaic process found in the most primal of eukaryotes.