Journal article
Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-022-32718-x
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 13
- Issue:
- 1
- Article number:
- 5174
- Publication date:
- 2022-09-02
- Acceptance date:
- 2022-08-09
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Keywords:
- Pubs id:
-
1277097
- Local pid:
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pubs:1277097
- Deposit date:
-
2022-09-04
- ARK identifier:
Terms of use
- Copyright holder:
- Zhou et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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