| First Author | Zhou D | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 5174 |
| PubMed ID | 36055998 | Mgi Jnum | J:328510 |
| Mgi Id | MGI:7335582 | Doi | 10.1038/s41467-022-32718-x |
| Citation | Zhou D, et al. (2022) Mapping autophagosome contents identifies interleukin-7 receptor-alpha as a key cargo modulating CD4+ T cell proliferation. Nat Commun 13(1):5174 |
| abstractText | CD4+ T cells are pivotal cells playing roles in the orchestration of humoral and cytotoxic immune responses. It is known that CD4+ T cell proliferation relies on autophagy, but identification of the autophagosomal cargo involved is missing. Here we create a transgenic mouse model, to enable direct mapping of the proteinaceous content of autophagosomes in primary cells by LC3 proximity labelling. Interleukin-7 receptor-alpha, a cytokine receptor mostly found in naive and memory T cells, is reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy show increased interleukin-7 receptor-alpha surface expression, while no defect in internalisation is observed. Mechanistically, excessive surface interleukin-7 receptor-alpha sequestrates the common gamma chain, impairing the interleukin-2 receptor assembly and downstream signalling crucial for T cell proliferation. This study shows that key autophagy substrates can be reliably identified in this mouse model and help mechanistically unravel autophagy's contribution to healthy physiology and disease. |
