Annexin A6 (AnxA6) has been implicated in cell signalling by contributing to the organisation of the plasma membrane. Here we examined whether AnxA6 regulates signalling and proliferation in T cells. We used a contact hypersensitivity model to immune challenge wild-type (WT) and AnxA6-/- mice and found that the in vivo proliferation of CD4 T cells, but not CD8+ T cells, was impaired in AnxA6-/- relative to WT mice. However, T-cell migration and signalling through the T-cell receptor ex vivo was similar between T cells isolated from AnxA6-/- and WT mice. In contrast, interleukin-2 (IL-2) signalling was reduced in AnxA6-/- compared with WT T cells. Further, AnxA6-deficient T cells had reduced membrane order and cholesterol levels. Taken together, our data suggest that AnxA6 regulates IL-2 homeostasis and sensitivity in T cells by sustaining a lipid raft-like membrane environment.
CITATION STYLE
Cornely, R., Pollock, A. H., Rentero, C., Norris, S. E., Alvarez-Guaita, A., Grewal, T., … Gaus, K. (2016). Annexin A6 regulates interleukin-2-mediated T-cell proliferation. Immunology and Cell Biology, 94(6), 543–553. https://doi.org/10.1038/icb.2016.15
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