Annexin A6 regulates interleukin‐2‐mediated T‐cell proliferation

Abstract

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.

α-Synuclein deficiency promotes neuroinflammation by increasing Th1 cell-mediated immune responses

“…In good agreement with this finding, we observed increased mRNA expression of IL-2 as central activator of T cell proliferation [19] in the spleen of aSyn −/− mice on day 10 after EAE induction, whereas mRNA expression of IL-4 as key cytokine during Th2 cell-mediated immune response was unaltered. These data suggest that α-synuclein deficiency leads to increased IL-2 production, thereby expanding the population of Th1 cells.…”

Annexins – insights from knockout mice

“…In agreement with earlier studies (Hawkins et al, 1999) (Cornely et al, 2016). To elicit an immune response, mice were then subjected to a delayed-type contact hypersensitivity reaction.…”

Annexin A6—A multifunctional scaffold in cell motility

“…30,111 Likewise, although our recent studies suggested that the absence of AnxA6 in T-lymphocytes destabilized the organization of the plasma membrane, T-cell migration and signaling was not affected in AnxA6-deficient T-lymphocytes. 63 Also, in chick midbrain neural crest cell development, AnxA6 depletion attenuated, while AnxA6 overexpression enhanced neural crest cell emigration, respectively. 112 However, opposing cellular activities as observed for AnxA6 are not uncommon, as loss of another scaffold protein, caveolin-1 (Cav-1), predicts poor clinical outcome in some cancers, while its overexpression is linked to aggressive and metastatic behavior in others.…”

“…54 Likewise, analysis of laurdan-stained T cells isolated from WT and AnxA6 ¡/¡ mice supported AnxA6 to alter the membrane environment in the plasma membrane. 63 From these observations we predicted consequences in the distribution of cell surface proteins. Indeed, PALM superresolution microscopy identified association of AnxA6 up/downregulation with differential and cell-specific differences in the cholesterol-sensitive microdomain distribution of membrane-anchored, fluorescent raft and nonraft marker proteins.…”