Academic Journal
Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation
| Τίτλος: | Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation |
|---|---|
| Συγγραφείς: | Zhou, D, Borsa, M, Puleston, DJ, Zellner, S, Capera, J, Sanderson, S, Schifferer, M, Hester, SS, Ge, X, Fischer, R, Jostins, L, Behrends, C, Alsaleh, G, Simon, AK |
| Στοιχεία εκδότη: | Springer Nature |
| Έτος έκδοσης: | 2022 |
| Συλλογή: | Oxford University Research Archive (ORA) |
| Περιγραφή: | 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. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| DOI: | 10.1038/s41467-022-32718-x |
| Διαθεσιμότητα: | https://doi.org/10.1038/s41467-022-32718-x https://ora.ox.ac.uk/objects/uuid:1bc2a694-a6db-4d4c-824c-b192448d9e64 |
| Rights: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Αριθμός Καταχώρησης: | edsbas.36B03B1A |
| Βάση Δεδομένων: | BASE |
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