Table 1.
Key examples for tissue-specific roles of autophagy pathways during autoimmunity.
| Related Disease/ Disease Model |
Type of Autophagy Impairment/Regulation of Autophagy |
Tissue | Effect | Disease Promoting (DP) or Disease Halting (DH) |
Ref. |
|---|---|---|---|---|---|
| EAE | Beclin 1 KO | T cells | Protection from onset of disease. | DP | [65] |
| MS | ↑ Atg5 transcripts and ATG5 protein in circulating and CNS-infiltrating T cells | T cells | ? | DP? | [72] |
| MS | ↑ Autophagy activity through EBV infection | B cells | EBV infection of B cells modulates the processing of a disease-relevant myelin autoantigen through autophagy. | DP | [80] |
| EAE | ATG7 KO | DCs | Amelioration of active EAE course due to impaired antigen presentation. | DP | [145] |
| EAE | ATG5 KO | DCs | Protection from onset of adoptively transferred disease due to insufficient reactivation of T cells. | DP | [84] |
| MS | ↑ Autophagosomes | Neurons (cerebellar dentate and the pontine nuclei) | Autophagy as neuron-autonomous mechanism of synaptic loss? | DP? | [96] |
| SLE | SNPs of autophagy related and associated genes: Atg5, Atg7, LRRK2, IRGM, DRAM1, CDKN1B, MTMR3, and APOL1 | – | Increased susceptibility to develop SLE. | DP? | [101-106] |
| SLE-like disease (mouse model) | ATG5 KO | DCs or B cells | Amelioration of SLE-like disease. | DP | [117] |
| SLE-like disease (mouse model) | ATG5 KO | DCs and B cells | Exacerbation of SLE-like disease. | (DP) | [118] |
| SLE | ↑ Autophagy activity (↑ LC3+ punctae) | B cells | Amount of LC3+ punctae correlates with disease score. Pharmacological inhibition of autophagy impairs plasmablast differentiation. | DP | [119] |
| SLE | ↓ Autophagy activity (↓ LC3+ protein levels) | Tregs | Impaired Treg differentiation and suppressive capacity. | DH | [121] |
| RA | ↑ Autophagy activity (↑ LC3+ protein levels) | RASF | Possible role in hypoxia-mediated upregulation of proinflammatory cytokine IL-6 in RA-FLS. | DP | [146] |
| RA | ↑ Autophagy activity (↑ LC3+, Beclin 1 protein levels) | RASF | Inverse correlation of autophagy protein levels and fraction of apoptotic cells in synovial tissues | DP | [147] |
| RA | ↑ Autophagy activity | RASF | IL-17-mediated disruption of mitochondrial respiration leads to upregulation of autophagy and resistance towards apoptosis | DP | [128] |
| RA | ↑ Autophagy activity | CD4+ T cells (pre-activated) | T cell hyperactivation and apoptosis resistance | DP | [134] |
| RA | ↓ Autophagy activity (due to PFKFB3 insufficiency) | CD4+ T cells (naïve – ex vivo activated) | Autophagy is not able to compensate cellular energy deficit caused by insufficient PFKFB3-mediated glucose metabolization | DH | [135] |
| RA | ↑ Autophagy activity | DCs, RASF | PAD-mediated citrullination of disease-relevant peptides | DP | [143,144] |