Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells

Schnurr, Max; Toy, Tracey; Shin, Amanda; Hartmann, Gunther; Rothenfußer, Simon; Soellner, Julia; Davis, Ian D.; Cebon, Jonathan; Maraskovsky, Eugene

doi:10.1182/blood-2003-06-1959

Cited by 166 publications

(144 citation statements)

References 45 publications

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“…In line with this hypothesis, leukemic PDCs express a wider profile of functional chemokine receptors than the normal circulating counterpart [46]. In addition to chemokines, adenosine and F2L, two agonists released by damaged tissues at the site of inflammation, have the ability to induce PDCs migration through the engagement of the adenosine receptor A1 and FPR3 (the formyl peptide receptor formerly known as FPRL2), respectively [47,48]. It was also reported that like MDCs, PDCs have functional receptors for the anaphylatoxins C3a and C5a [49].…”

Section: Reviewmentioning

confidence: 88%

Trafficking properties of plasmacytoid dendritic cells in health and disease

Sozzani

Vermi

Prete

et al. 2010

Trends in Immunology

145

151

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Section: Reviewmentioning

confidence: 88%

Trafficking properties of plasmacytoid dendritic cells in health and disease

Sozzani

Vermi

Prete

et al. 2010

Trends in Immunology

145

151

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“…It has been described that both types of ADA-anchoring proteins are expressed in DC (20)(21)(22)(23)(24)(25). The monocyte-derived DC used in this work express ADA-anchoring proteins at the mRNA and protein levels.…”

Section: Resultsmentioning

confidence: 99%

“…It should also be noted that CD26 is expressed on a restricted subpopulation of DC from afferent lymph and lymph nodes (20), whereas the AR are expressed in myeloid DC (21-24) as much as in plasmacytoid DC (25), which are the two major known subsets of DC.…”

mentioning

confidence: 99%

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse

Pacheco

Martinez-Navío

Lejeune

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

221

192

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Adenosine deaminase (ADA), a protein whose deficit leads to severe combined immunodeficiency, binds to the cell surface by means of either CD26, A 1 adenosine receptors, or A2B adenosine receptors. The physiological role of these interactions is not well understood. Our results show that by a 3-fold reduction in the EC 50 for the antigen, ADA potentiated T cell proliferation in autologous cocultures with antigen-pulsed immature or mature dendritic cells. Costimulation was not due to the enzymatic activity but to the interaction of ADA-CD26 complexes in T cells with an ADAanchoring protein in dendritic cells. From colocalization studies, it is deduced that ADA colocalizing with adenosine receptors on dendritic cells interact with CD26 expressed on lymphocytes. This costimulatory signal in the immunological synapse leads to a marked increase (3-to 34-fold) in the production of the T helper 1 and proimmflamatory cytokines IFN-␥, TNF-␣, and IL-6. adenosine deaminase ͉ costimulation ͉ immunosynapse A denosine deaminase (ADA; EC 3.5.4.4) an enzyme involved in purine metabolism, catalyzes the hydrolytic deamination of adenosine or 2Ј-deoxyadenosine to inosine or 2Ј-deoxyinosine and ammonia. Congenital defect of ADA causes severe combined immunodeficiency, which is characterized by the absence of functional T and B lymphocytes in affected individuals (1). For many years, ADA was considered to be cytosolic, but it has been found on the cell surface of many cell types; therefore, it can be considered an ectoenzyme. In addition, ecto-ADA has been proposed to have a catalytic-independent function as a costimulatory molecule in lymphocytes (2).So far, two types of surface anchoring proteins for ecto-ADA have been described. The first type, with only one member, is CD26, a multifunctional protein of 110 KDa strongly expressed on epithelial cells (kidney proximal tubules, intestine, and bile duct) and on several types of endothelial cells and fibroblasts and on leukocyte subsets (3-5). The second type of ecto-ADA-binding proteins includes the adenosine receptors (AR) A 1 (A 1 R) (6) and A 2B (A 2B R) (7). The association between ADA and CD26 on the T cell surface has been proposed to have a costimulatory function during T cell antigen receptor-CD3 complex engagement (2). Because CD26 has a short cytoplasmatic tail, it needs partners to transduce the signal. Ishii et al. (8) have described that CD26-mediated signaling occurs through its association with CD45RO. At present, it is not known whether ADA generates a signal when it binds to AR. However, we have previously demonstrated that ADA binding to A 1 R or A 2B R is required for high efficiency affinity binding of the agonist and for efficient agonist-dependent signaling (6, 7).Dendritic cells (DC) are the most potent antigen-presenting cells (APC) specialized in the initiation of immune responses by directing the activation and differentiation of naïve T lymphocytes (9, 10). Immature DC (iDC) reside in most tissues to uptake antigen; they are engaged when exposed to danger ...

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“…Moreover, A 2A R blockade actually exacerbates tissue damage involving inflammatory reactions in the periphery (reviewed in [295,296]), instead of the tissue protection, as observed in noxious brain conditions. Furthermore, all studies available indicate that the activation of A 2A Rs inhibits the release of pro-inflammatory cytokines from inflammatory cells, such as macrophages (e.g., [223, 314Y316]), dendritic cells [220,221], monocytes [317Y319] or T cells [320,321]. This latter cell type, in particular CD4 + T cells, are most relevant since it was recently shown that the key role of A 2A Rs in attenuating peripheral tissue damage from ischemiaYreperfusion injury is due to the activation of A 2A Rs in CD4 + T cells [322].…”

Section: A 2a Receptor Blockade Confers Robust Neuroprotectionmentioning

confidence: 99%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

483

432

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Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A 1 receptors (A 1 Rs) and the less abundant, but widespread, facilitatory A 2A Rs. It is commonly assumed that A 1 Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A 1 R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A 1 Rs in chronic noxious situations. In contrast, A 2A Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A 2A R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A 2A R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A 2A R blockade compared to A 1 R activation does not mean that A 1 R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A 2A R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A 1 Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.Abbreviations: Ab -b-amyloid peptide; A 1 Rs -A 1 receptors; A 2A Rs -A 2A

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Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells

Cited by 166 publications

References 45 publications

Trafficking properties of plasmacytoid dendritic cells in health and disease

Trafficking properties of plasmacytoid dendritic cells in health and disease

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

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