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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.

Original publication

DOI

10.1038/s41467-022-32718-x

Type

Journal article

Journal

Nat Commun

Publication Date

02/09/2022

Volume

13

Keywords

Animals, Autophagosomes, CD4-Positive T-Lymphocytes, Cell Proliferation, Interleukin-2, Interleukin-7, Lymphocyte Activation, Mice, Receptors, Interleukin-7