Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation

Zhou, D.; Borsa, M.; Puleston, D.J.; Zellner, S.; Capera, J.; Sanderson, S.; Schifferer, M.; Hester, S.S.; Ge, X.; Fischer, R.; Jostins, L.; Behrends, C.; Alsaleh, G.; Simon, A.K.

Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation

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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., Borsa, M., Puleston, D.J., Zellner, S., Capera, J., Sanderson, S., Schifferer, M., Hester, S.S., Ge, X., Fischer, R., Jostins, L., Behrends, C., 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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