Annexin-1 modulates T-cell activation and differentiation

D’Acquisto, Fulvio; Merghani, Ahmed; Lecona, Emilio; Rosignoli, Guglielmo; Raza, Karim; Buckley, Christopher D.; Flower, Roderick J.; Perretti, Mauro

doi:10.1182/blood-2006-05-022798

Cited by 153 publications

(177 citation statements)

References 48 publications

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“…Several studies provide evidence that AnxA1 acts to inhibit T cell-dependent models of inflammation (13)(14)(15)(16). In contrast, other studies suggest that AnxA1 plays a facilitatory role in T cell-mediated responses (17)(18)(19). The reasons for these divergent data are unclear, but the complexity of CD4 + T cell-mediated immune responses may be a contributing factor.…”

mentioning

confidence: 62%

“…Moreover, it is unclear whether the effects of AnxA1 on T cell-mediated inflammatory responses arise from effects of AnxA1 expressed specifically by T cells. AnxA1 has been shown to affect activation of several of the myriad signaling pathways associated with T cell activation, including Akt, p38 and ERK MAPK, and NF-kB (17,18,(24)(25)(26)(27). However, these effects have not been observed specifically in CD4 + T cells in the context of Ag-induced activation.…”

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confidence: 76%

“…In contrast, studies using murine T cells indicate that exogenous AnxA1 promotes Th1 development while inhibiting development of Th2 cells (17). This was supported by in vivo studies in the Th1/Th17-mediated collagen-induced arthritis (CIA) model in mice, which was exacerbated by administration of exogenous AnxA1 (17). Conversely, AnxA1-deficient mice showed reduced inflammation in a Th1/Th17-mediated model of experimental allergic encephalomyelitis, as well as exacerbation of Th2-mediated responses (18,19).…”

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confidence: 95%

“…Studies using human PBMCs from atopic individuals revealed that exogenous AnxA1-derived peptides inhibit Th cell proliferation and differentiation, reducing Ag-stimulated release of both Th1 and Th2 cytokines (16). In contrast, studies using murine T cells indicate that exogenous AnxA1 promotes Th1 development while inhibiting development of Th2 cells (17). This was supported by in vivo studies in the Th1/Th17-mediated collagen-induced arthritis (CIA) model in mice, which was exacerbated by administration of exogenous AnxA1 (17).…”

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confidence: 99%

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Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Yang

Song

Deane

et al. 2013

The Journal of Immunology

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Annexin A1 (AnxA1) is recognized as an endogenous anti-inflammatory molecule. However, its effects on the adaptive immune response and, in particular, on T cells remain unclear. In this study, we investigated the actions of AnxA1 in three distinct models of T cell–mediated inflammation. In contact hypersensitivity, collagen-induced arthritis, and inflammation induced by OT-II TCR transgenic T cells responding to OVA, AnxA1 deficiency significantly increased Ag-induced T cell proliferation and the resultant level of inflammation. In the contact hypersensitivity model, this was associated with increased adhesion of CD4+ T cells, CD8+ T cells, and neutrophils in the dermal microvasculature, as well as increased T cell expression of RORγt and IL-17A. In collagen-induced arthritis, deficiency of endogenous AnxA1 increased susceptibility to arthritis and Ag-specific T cell activation. Deficiency of AnxA1 also increased OVA-induced cutaneous delayed-type hypersensitivity and IFN-γ and IL-17 release. Transfer experiments using CD4+ T cells from AnxA1−/− mice demonstrated that the absence of AnxA1 solely in T cells resulted in increased inflammatory responses in wild-type recipients. Similarly, experiments using AnxA1−/− OT-II CD4+ T cells demonstrated that the absence of AnxA1 in T cells was sufficient to induce increased Ag-specific CD4+ T cell proliferation in vivo, augment T cell production of IFN-γ, IL-17, TNF, and IL-6, and increase Akt, ERK, and p38 activation. Together, these findings indicate that T cell–expressed AnxA1 functions to attenuate T cell–driven inflammatory responses via T cell–intrinsic effects on intracellular signaling, proliferation, and Th1/Th17 cytokine release.

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confidence: 62%

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confidence: 76%

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confidence: 95%

mentioning

confidence: 99%

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Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Yang

Song

Deane

et al. 2013

The Journal of Immunology

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“…The accumulation of Annexin 1 and its presentation to particular leukocyte subsets can have broad immune outcomes. For example, Annexin 1-loaded NPs may reduce neutrophils via induction of apoptosis [69] and/or promote T cell activation [70].…”

Section: Removal Of Inflammatory Mediators and Specific Toxinsmentioning

confidence: 99%

Harnessing Nanoparticles for Immune Modulation

Getts¹,

Shea²,

Miller³

et al. 2016

Trends in Immunology

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Recent approaches using nanoparticles engineered for immune regulation have yielded promising results in preclinical models of disease. The number of nanoparticle therapies is growing, fueled by innovations in nanotechnology and advances in understanding of the underlying pathogenesis of immune-mediated diseases. In particular, recent mechanistic insight into the ways in which nanoparticles interact with the mononuclear phagocyte system and impact its function during homeostasis and inflammation have highlighted the potential of nanoparticle-based therapies for controlling severe inflammation while concurrently restoring peripheral immune tolerance in autoimmune disease. Here we review recent advances in nanoparticle-based approaches aimed at immune-modulation, and discuss these in the context of concepts in polymeric nanoparticle development, including particle modification, delivery and the factors associated with successful clinical deployment.

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Impaired T cell activation and increased Th2 lineage commitment in Annexin‐1‐deficient T cells

et al. 2007

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Annexin-1 is a well-known endogenous anti-inflammatory protein that modulates the activation of cells of the innate immune system such as neutrophils and macrophages. We have recently reported a positive role for the exogenous protein on T cell differentiation, however, whether such a role holds true for the endogenous protein has yet to be determined. This aspect has been investigated here finding that Annexin-1-deficient T cells display an impaired activation and proliferation in response to anti-CD3 plus anti-CD28 stimulation. Furthermore, differentiation of T cells from Annexin-1-deficient mice in Th0/Th1/Th2 or Th17 skewing conditions demonstrated an increased Th2 phenotype compared to cells from control littermates. Similar results were obtained when we analyzed the Th1/Th2 profile of lymph node cells obtained from mice immunized with keyhole limpet hemocyanin or the inflammatory infiltrate in mouse model of allergic inflammation. These results demonstrate a novel modulatory role of endogenous Annexin-1 in TCR signaling and T cell differentiation and suggest this protein might play a dual and complementary role in the innate and adaptive immune response.

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Annexin-1 modulates T-cell activation and differentiation

Abstract: Annexin-1 is an anti-inflammatory protein that plays an important homeostatic role in innate immunity; however, its potential actions in the modulation of adaptive immunity have never been explored.

Cited by 153 publications

References 48 publications

Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation

Harnessing Nanoparticles for Immune Modulation

Impaired T cell activation and increased Th2 lineage commitment in Annexin‐1‐deficient T cells

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