Autophagy in dendritic cells

Abstract

Autophagy and immunity share the property of being auto-protective for the organism. Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. Perturbations in autophagy are associated with inflammation and cancer development. Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells. Among these, dendritic cells (DCs) are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer. DCs undergo functional maturation that can either lead to an immunostimulatory phenotype, as in the context of infection, or to a tolerogenic phenotype associated with immunosuppression to self-antigens, as well as to cancer. An increasing number of recent studies has characterized the involvement of autophagy in DC functions in various physiological and pathological contexts. Here, we provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology.

Keywords: autophagy; dendritic cells; maturation.

Figure 1

Scheme of the autophagic machinery described in DCs. The dynamic assembly and interactions of ATG proteins are highlighted: the ULK1 complex, class III PI3K complex and ubiquitin-like conjugation systems for ATG5-ATG12-ATG16 complex and the recruitment of LC3 to autophagosomal membranes. The thick arrows indicate trafficking routes, and the thin arrows indicate enzymatic reactions.

Figure 2

Scheme describing the involvement of ATG genes in the functional aspects of DC maturation. Each step of DC functional maturation is described with the ATG proteins reported to be involved in their regulation. See Table 1 for references. LN: lymph node; MHC-II: major histocompatibility complex class II; PAMP: pathogen-associated molecular patterns; TCR: T-cell receptor; TLR: Toll-like receptor.