The role of adenosinergic pathway in human autoimmune diseases

Dong, Ke; Gao, Zhaowei; Zhang, Huizhong

doi:10.1007/s12026-016-8870-2

Cited by 33 publications

(32 citation statements)

References 54 publications

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“…Thus, down-regulation of CD73 on B cells might tip the balance toward higher AMP concentrations and lower ADO concentrations. It is important to note that different studies have shown that a disturbance in the adenosinergic pathway can lead to an imbalance of pro-and anti-inflammatory effects depending on the local environment and ADO concentration [58,[60][61][62]; therefore, our data add to the hypothesis that lower concentrations of ADO might be detrimental by causing the increased chronic immune activation observed during chronic HIV infection [2,63].…”

Section: Discussionsupporting

confidence: 52%

Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression

Kim

Ackermann

Tóth

et al. 2017

Journal of Leukocyte Biology

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Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral ( = 70) and lymph nodal B cells ( = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells ( < 0.001) compared with healthy controls. Decreased frequencies of CD39CD73 B cells in patients with HIV correlated with low CD4 counts ( < 0.0256) as well as increased proliferation and exhaustion status as determined by Ki-67 and programmed death-1 expression. Down-regulation of CD73 was observed in naive and memory B cells as determined by CD27 and CD21. Neither HIV elite controller patients nor antiretroviral therapy-treated patients had significantly lower CD39 and CD73 expression on B cells compared with healthy controls. Of importance, low CD73 expression on B cells was associated with modulated in vitro B cell function. Further in vivo studies are warranted to evaluate the in vivo role of phenotypic loss of CD73 in B cell dysregulation in HIV.

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Section: Discussionsupporting

confidence: 52%

Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression

Kim

Ackermann

Tóth

et al. 2017

Journal of Leukocyte Biology

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“…Deletion of CD39 and CD73 leads to higher levels of anti-RNP antibodies in response to pristane, with CD73 deletion in particular promoting expansion of splenic B cell and T cell populations that likely contribute to autoantibody production. Within the T cell compartment, it is notable that some of these changes (expansion of effector/memory T cells and T H 17 cells) were present independent of pristane administration, which would fit with a general predisposition toward inflammation and autoimmunity conferred by loss of ectonucleotidase activity ( 11 , 39 , 40 ). For example, protective roles for ectonucleotidases have been suggested in rheumatoid arthritis ( 41 , 42 ), juvenile idiopathic arthritis ( 43 ), inflammatory bowel disease ( 44 , 45 ), autoimmune hepatitis ( 46 ), and atherosclerosis ( 47 , 48 ).…”

Section: Discussionmentioning

confidence: 99%

Ectonucleotidase-Mediated Suppression of Lupus Autoimmunity and Vascular Dysfunction

et al. 2018

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ObjectivesCD39 and CD73 are surface enzymes that jut into the extracellular space where they mediate the step-wise phosphohydrolysis of the autocrine and paracrine danger signals ATP and ADP into anti-inflammatory adenosine. Given the role of vascular and immune cells’ “purinergic halo” in maintaining homeostasis, we hypothesized that the ectonucleotidases CD39 and CD73 might play a protective role in lupus.MethodsLupus was modeled by intraperitoneal administration of pristane to three groups of mice: wild-type (WT), CD39−/−, and CD73−/−. After 36 weeks, autoantibodies, endothelial function, kidney disease, splenocyte activation/polarization, and neutrophil activation were characterized.ResultsAs compared with WT mice, CD39−/− mice developed exaggerated splenomegaly in response to pristane, while both groups of ectonucleotidase-deficient mice demonstrated heightened anti-ribonucleoprotein production. The administration of pristane to WT mice triggered only subtle dysfunction of the arterial endothelium; however, both CD39−/− and CD73−/− mice demonstrated striking endothelial dysfunction following induction of lupus, which could be reversed by superoxide dismutase. Activated B cells and plasma cells were expanded in CD73−/− mice, while deficiency of either ectonucleotidase led to expansion of TH17 cells. CD39−/− and CD73−/− mice demonstrated exaggerated neutrophil extracellular trap release, while CD73−/− mice additionally had higher levels of plasma cell-free DNA.ConclusionThese data are the first to link ectonucleotidases with lupus autoimmunity and vascular disease. New therapeutic strategies may harness purinergic nucleotide dissipation or signaling to limit the damage inflicted upon organs and blood vessels by lupus.

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“…Purinergic signaling is highly described in tumoral context ( 162 ) and in autoimmune diseases ( 163 ) but poorly studied in the context of cardiac pathologies. Given the high production rate of ATP and the turnover required to maintain its continuous mechanical work, disruption of heart tissue generates the release of high amounts of ATP to the extracellular space.…”

Section: Signaling Pathways and Molecules Modulating Cardiovascular Imentioning

confidence: 99%

New Insights into the Immunobiology of Mononuclear Phagocytic Cells and Their Relevance to the Pathogenesis of Cardiovascular Diseases

et al. 2018

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Macrophages are the primary immune cells that reside within the myocardium, suggesting that these mononuclear phagocytes are essential in the orchestration of cardiac immunity and homeostasis. Independent of the nature of the injury, the heart triggers leukocyte activation and recruitment. However, inflammation is harmful to this vital terminally differentiated organ with extremely poor regenerative capacity. As such, cardiac tissue has evolved particular strategies to increase the stress tolerance and minimize the impact of inflammation. In this sense, growing evidences show that mononuclear phagocytic cells are particularly dynamic during cardiac inflammation or infection and would actively participate in tissue repair and functional recovery. They respond to soluble mediators such as metabolites or cytokines, which play central roles in the timing of the intrinsic cardiac stress response. During myocardial infarction two distinct phases of monocyte influx have been identified. Upon infarction, the heart modulates its chemokine expression profile that sequentially and actively recruits inflammatory monocytes, first, and healing monocytes, later. In the same way, a sudden switch from inflammatory macrophages (with microbicidal effectors) toward anti-inflammatory macrophages occurs within the myocardium very shortly after infection with Trypanosoma cruzi, the causal agent of Chagas cardiomyopathy. While in sterile injury, healing response is necessary to stop tissue damage; during an intracellular infection, the anti-inflammatory milieu in infected hearts would promote microbial persistence. The balance of mononuclear phagocytic cells seems to be also dynamic in atherosclerosis influencing plaque initiation and fate. This review summarizes the participation of mononuclear phagocyte system in cardiovascular diseases, keeping in mind that the immune system evolved to promote the reestablishment of tissue homeostasis following infection/injury, and that the effects of different mediators could modulate the magnitude and quality of the immune response. The knowledge of the effects triggered by diverse mediators would serve to identify new therapeutic targets in different cardiovascular pathologies.

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The role of adenosinergic pathway in human autoimmune diseases

Cited by 33 publications

References 54 publications

Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression

Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression

Ectonucleotidase-Mediated Suppression of Lupus Autoimmunity and Vascular Dysfunction

New Insights into the Immunobiology of Mononuclear Phagocytic Cells and Their Relevance to the Pathogenesis of Cardiovascular Diseases

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