Dataset Information

Mapping of the autophagosomal degradome identifies IL-7Rα as key 1 cargo in proliferating CD4+ T-cells

ABSTRACT: CD4+ T cells orchestrate both humoral and cytotoxic immune responses. While it is known that CD4+ T cell proliferation relies on autophagy, direct identification of the autophagosomal cargo involved is still missing. Here, we created a transgenic mouse model, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell by LC3 proximity labelling. IL-7Rα, a cytokine receptor mostly found in naïve and memory T cells, was reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy showed increased IL-7Rα surface expression, while no defect in internalisation was observed. Mechanistically, excessive surface IL-7Rα sequestrates the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. This study provides proof-of-principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy’s contribution to healthy physiology and disease.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cytotoxic T-lymphocyte Protein 4 (mouse), Mef Cell

SUBMITTER: Roman Fischer

LAB HEAD: Roman Fischer

PROVIDER: PXD033733 | Pride | 2022-07-08

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	FL1317_MSQ2103_20210129_DZhou_1_Ctrl1.raw	Raw
	FL1317_MSQ2103_20210129_DZhou_2_ctrl2.raw	Raw
	FL1317_MSQ2103_20210129_DZhou_3_ctrl3.raw	Raw
	FL1317_MSQ2103_20210129_DZhou_4_RAPI1.raw	Raw
	FL1317_MSQ2103_20210129_DZhou_5_RAPI2.raw	Raw

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Publications

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

Zhou Dingxi D Borsa Mariana M Puleston Daniel J DJ Zellner Susanne S Capera Jesusa J Sanderson Sharon S Schifferer Martina M Hester Svenja S SS Ge Xin X Fischer Roman R Jostins Luke L Behrends Christian C Alsaleh Ghada G Simon Anna Katharina AK

Nature communications 20220902 1

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 reproducib ...[more]

PMID: 36055998

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