Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation
| Autor: | Dingxi Zhou, Mariana Borsa, Daniel J. Puleston, Susanne Zellner, Jesusa Capera, Sharon Sanderson, Martina Schifferer, Svenja S. Hester, Xin Ge, Roman Fischer, Luke Jostins, Christian Behrends, Ghada Alsaleh, Anna Katharina Simon |
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| Rok vydání: | 2022 |
| Předmět: |
metabolism [Interleukin-2]
CD4-Positive T-Lymphocytes Receptors Interleukin-7 Multidisciplinary metabolism [Interleukin-7] Interleukin-7 Autophagosomes General Physics and Astronomy General Chemistry Lymphocyte Activation metabolism [Autophagosomes] General Biochemistry Genetics and Molecular Biology Mice Cardiovascular and Metabolic Diseases metabolism [Receptors Interleukin-7] Animals Interleukin-2 ddc:500 Cell Proliferation |
| Zdroj: | Nature Communications 13(1), 5174 (2022). doi:10.1038/s41467-022-32718-x |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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