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

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-alpha, a cytokine receptor mostly found in naive 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-alpha surface expression, while no defect in internalisation is observed. Mechanistically, excessive surface interleukin-7 receptor-alpha 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. Autophagy is known to impact CD4+ T cell proliferation but the identity of autophagosomal components remain unclear. Here the authors leverage a transgenic mouse model to assess the autophagosomal compartment and identify interleukin-7 receptor-alpha as a key cargo in proliferating CD4+ T cells.

Automated summary

This study identifies interleukin-7 receptor-alpha as a key cargo in proliferating CD4+ T cells within the autophagosomal compartment using a transgenic mouse model. Moreover, the authors uncover the mechanism by which excessive surface interleukin-7 receptor-alpha affects T cell proliferation.