CD38 and CD157 Ectoenzymes Mark Cell Subsets in the Human Corneal Limbus

Horenstein, Alberto L.; Sizzano, Federico; Lusso, Riccardo; Besso, Federico Genzano; Ferrero, Enza; Deaglio, Silvia; Corno, F; Malavasi, Fabio

doi:10.2119/molmed.2008.00108

Cited by 44 publications

(23 citation statements)

References 41 publications

(33 reference statements)

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“…On the other side, the interplay between adenosine and purinergic receptors generates local cellular anergy, which is a relevant mechanism of peripheral tolerance in both normal tissues and in the course of oncogenesis and tumor progression 52 . Therefore, the NAD + -catalytic network that we delineated here is now under evaluation in normal cells (natural killer cells, mesenchymal stem cells, Tregs, regulatory B cells, and myeloid-derived suppressor cells) as well as in the human cornea, which was selected because of its immunologically privileged status and proven expression of CD38 (and CD157) 55 . The results of these studies will indicate whether this adenosinergic ectoenzyme network contributes to the generation of local tolerance or rather facilitates the elicitation of adaptive immune responses.…”

Section: Discussionmentioning

confidence: 99%

A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes

Chillemi²,

et al. 2013

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The tumor microenvironment is characterized by of high levels of extracellular nucleotides that are metabolized through the dynamic and sequential action of cell surface enzymes (ectoenzymes). These ectoenzymes operate according to their spatial arrangement, as part of (1) continuous (molecules on the same cell) or (2) discontinuous (molecules on different cells) pathways, the latter being facilitated by restricted cellular microenvironment. The outcome of this catabolic activity is an increase in the local concentration of adenosine, a nucleoside involved in the control of inflammation and immune responses. The aim of the work presented here was to demonstrate that a previously unexplored enzymatic pathway may be an alternate route to produce extracellular adenosine. Our data show that this new axis is driven by the nucleotide-metabolizing ectoenzymes CD38 (an NAD+ nucleosidase), the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, also known as CD203a or PC-1) and the 5′ ectonucleotidase (5′-NT) CD73, while bypassing the canonical catabolic pathway mediated by the nucleoside tri- and diphosphohydrolase (NTPDase) CD39. To determine the relative contributions of these cell surface enzymes to the production of adenosine, we exploited a human T-cell model allowing for the modular expression of the individual components of this alternative pathway upon activation and transfection. The biochemical analysis of the products of these ectoenzymes by high-performance liquid chromatography (HPLC) fully substantiated our working hypothesis. This newly characterized pathway may facilitate the emergence of an adaptive immune response in selected cellular contexts. Considering the role for extracellular adenosine in the regulation of inflammation and immunogenicity, this pathway could constitute a novel strategy of tumor evasion, implying that these enzymes may represent ideal targets for antibody-mediated therapy.

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Section: Discussionmentioning

confidence: 99%

A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes

Chillemi²,

et al. 2013

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“…These findings indicated that human LSC express p63, however, because of the nuclear expression of p63, further enrichment of the limbal grafts for p63 purity was not feasible, leaving unanswered the question whether a pure p63+ population could have resulted in more universal therapeutic success, as might be expected of an autologous LSC graft. Subsequently, several additional potential human LSC markers were described based on their anatomical and immunohistochemical association with p63, including positive selection markers Lgr5, Tcf4, CD157, CD71 low /Integrin α6 high , TrkA, N‐Cadherin, Abcg2, and Cytokeratin15, and negative selection markers Cytokeratin 3, ALDH dim , RHAMM bright , and Connexin‐43 (Table ).…”

Section: Limbal Stem Cell Identitymentioning

confidence: 99%

Limbal stem cells: identity, developmental origin, and therapeutic potential

González

Sasamoto

Ksander

et al. 2017

WIREs Developmental Biology

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The cornea is our window to the world and our vision is critically dependent on corneal clarity and integrity. Its epithelium represents one of the most rapidly regenerating mammalian tissues, undergoing full-turnover over the course of approximately 1-2 weeks. This robust and efficient regenerative capacity is dependent on the function of stem cells residing in the limbus, a structure marking the border between the cornea and the conjunctiva. Limbal stem cells (LSC) represent a quiescent cell population with proliferative capacity residing in the basal epithelial layer of the limbus within a cellular niche. In addition to LSC, this niche consists of various cell populations such as limbal stromal fibroblasts, melanocytes and immune cells as well as a basement membrane, all of which are essential for LSC maintenance and LSC-driven regeneration. The LSC niche's components are of diverse developmental origin, a fact that had, until recently, prevented precise identification of molecularly defined LSC. The recent success in prospective LSC isolation based on ABCB5 expression and the capacity of this LSC population for long-term corneal restoration following transplantation in preclinical in vivo models of LSC deficiency underline the considerable potential of pure LSC formulations for clinical therapy. Additional studies, including genetic lineage tracing of the developmental origin of LSC will further improve our understanding of this critical cell population and its niche, with important implications for regenerative medicine. WIREs Dev Biol 2018, 7:e303. doi: 10.1002/wdev.303 This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration.

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“…Many putative corneal epithelial stem cell markers (e.g. p63, ABCG2, Integrin a9, Keratin 15, N-cadherin, NGF/TrkA, Integrin a6/CD71, Hes1, p75, Nectin 3, Importin 13, Nucleostemin, CD38/157, Lrig1, ABCB5, WNT7A) have been reported worldwide (Di Girolamo et al, 2008;Hayashi et al, 2008Hayashi et al, , 2007Horenstein et al, 2009;Kawashima et al, 2009;Ksander et al, 2014;Kusanagi et al, 2009;Nakamura et al, 2014Nakamura et al, , 2008aOuyang et al, 2014;Pajoohesh-Ganji et al, 2006;Pellegrini et al, 2001;Qi et al, 2008;Wang et al, 2009;Watanabe et al, 2004;Yoshida et al, 2006) (Fig. 10).…”

Section: Candidate Limbal Stem Cell Markersmentioning

confidence: 99%