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| Item Type: | Article |
|---|---|
| Title: | Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation |
| Creators Name: | Zhou, D. and Borsa, M. and Puleston, D.J. and Zellner, S. and Capera, J. and Sanderson, S. and Schifferer, M. and Hester, S.S. and Ge, X. and Fischer, R. and Jostins, L. and Behrends, C. and Alsaleh, G. and Simon, A.K. |
| Abstract: | 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-α, a cytokine receptor mostly found in naïve 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-α surface expression, while no defect in internalisation is observed. Mechanistically, excessive surface interleukin-7 receptor-α 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. |
| Keywords: | Autophagosomes, CD4-Positive T Cells, Cytokines, Protein–Protein Interaction Networks, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 13 |
| Number: | 1 |
| Page Range: | 5174 |
| Date: | 2 September 2022 |
| Official Publication: | https://doi.org/10.1038/s41467-022-32718-x |
| PubMed: | View item in PubMed |
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