Immunologic manifestations of autophagy
Vojo Deretic, … , Santosh Chauhan, Michael Mandell
Vojo Deretic, … , Santosh Chauhan, Michael Mandell
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(1):75-84. https://doi.org/10.1172/JCI73945.
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Review

Immunologic manifestations of autophagy

Abstract

The broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. The immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique immunologic adaptations. One of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and includes a stratified array of nearly all principal immunologic processes. This Review summarizes the broad immunologic roles of autophagy. Furthermore, it uses the autophagic control of Mycobacterium tuberculosis as a paradigm to illustrate the breadth and complexity of the immune effects of autophagy.

Authors

Vojo Deretic, Tomonori Kimura, Graham Timmins, Pope Moseley, Santosh Chauhan, Michael Mandell

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Figure 2

Autophagy affects lymphocyte development and function.

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Autophagy affects lymphocyte development and function. Autophagy affects...
Autophagy affects self-renewal of HSCs, plasma cell survival, IgG secretion, survival of a special type of B cell, B1, and maintenance of memory B cells (not shown). Autophagy affects T cell survival following TCR activation and controls stability of immunologic synapses; it also controls innate immune cell (e.g., macrophage) signaling by suppressing ROS via the removal of depolarized mitochondria and inhibition of IL-1 release that influences, along with the durability of immunologic synapses, polarization of T cells into a Th17 phenotype. Autophagy also affects selection of naive T cell repertoire in the thymus by self antigen processing and presentation and survival and functionality of maturing T cells by trimming mitochondria and ER, thus ensuring Ca2+ homeostasis. Red crescents symbolize the entire autophagy pathway.