Variable impact of CD39 in experimental murine colitis

Beat M Kunzli, Pascal O Berberat, Karen M Dwyer, Silvia Deaglio, Eva Csizmadia, Peter J Cowan, Anthony J F D'Apice, Gregory Thomas Charles Moore, Keiichi Enjyoji, Helmut Friess, Simon Christopher Robson

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18 Citations (Scopus)

Abstract

BACKGROUND: Dysregulation of immune responses in inflammatory bowel diseases (IBD) results in intestinal inflammation and vascular injury while exacerbating systemic disease. CD39 is an ectonucleotidase, expressed by T regulatory cells and dendritic cells, that hydrolyzes extracellular nucleotides to modify those cellular immune responses implicated in IBD. Genetic polymorphisms of CD39 have been linked to Crohn s disease while gene deletion in mice exacerbates dextran sodium sulphate-induced colitis. AIM: The aim of this study was to test how global deletion of CD39 in mice impacts other models of experimental colitis. METHODS: Colitis was induced in CD39-null and -wt mice, using trinitrobenzene sulfonic acid (TNBS, 125 mg/kg) administered intrarectally. Oxazolone colitis (1.5 oxazolone in 50 alcohol) was induced in comparable groups. Morphology, clinical and molecular parameters, and FACS analyses of lamina propria mononuclear cells (LPMC) were examined in CD39-null mice. CD39 expression was analyzed in human IBD biopsies. RESULTS: Paradoxically, TNBS colitis in CD39-null mice was characterized by improved survival, favorable clinical scores, and decreased MPO activity, when compared to wt mice (P <0.05). LPMC from TNBS colitis contained significantly increased amounts of T-cells (CD3(+) and CD4(+)) and TNF-alpha mRNA expression were increased over those in CD39 null mice (P <0.05). In contrast, oxazolone treated CD39-null and wt mice had comparable outcomes. In both ulcerative colitis and Crohn s disease, CD39 is present at high levels in intestinal tissue biopsies. CONCLUSIONS: TNBS colitis was attenuated in CD39-null mice whereas oxazolone-induced colitis was not impacted. Impaired adaptive cellular immune reactivity in the CD39-null environment appears protective in hapten-mediated Th1-type colitis. CD39 is expressed at high levels in clinical IBD tissues.
Original languageEnglish
Pages (from-to)1393 - 1403
Number of pages11
JournalDigestive Diseases and Sciences
Volume56
Issue number5
DOIs
Publication statusPublished - 2011

Cite this

Kunzli, B. M., Berberat, P. O., Dwyer, K. M., Deaglio, S., Csizmadia, E., Cowan, P. J., ... Robson, S. C. (2011). Variable impact of CD39 in experimental murine colitis. Digestive Diseases and Sciences, 56(5), 1393 - 1403. https://doi.org/10.1007/s10620-010-1425-9
Kunzli, Beat M ; Berberat, Pascal O ; Dwyer, Karen M ; Deaglio, Silvia ; Csizmadia, Eva ; Cowan, Peter J ; D'Apice, Anthony J F ; Moore, Gregory Thomas Charles ; Enjyoji, Keiichi ; Friess, Helmut ; Robson, Simon Christopher. / Variable impact of CD39 in experimental murine colitis. In: Digestive Diseases and Sciences. 2011 ; Vol. 56, No. 5. pp. 1393 - 1403.
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abstract = "BACKGROUND: Dysregulation of immune responses in inflammatory bowel diseases (IBD) results in intestinal inflammation and vascular injury while exacerbating systemic disease. CD39 is an ectonucleotidase, expressed by T regulatory cells and dendritic cells, that hydrolyzes extracellular nucleotides to modify those cellular immune responses implicated in IBD. Genetic polymorphisms of CD39 have been linked to Crohn s disease while gene deletion in mice exacerbates dextran sodium sulphate-induced colitis. AIM: The aim of this study was to test how global deletion of CD39 in mice impacts other models of experimental colitis. METHODS: Colitis was induced in CD39-null and -wt mice, using trinitrobenzene sulfonic acid (TNBS, 125 mg/kg) administered intrarectally. Oxazolone colitis (1.5 oxazolone in 50 alcohol) was induced in comparable groups. Morphology, clinical and molecular parameters, and FACS analyses of lamina propria mononuclear cells (LPMC) were examined in CD39-null mice. CD39 expression was analyzed in human IBD biopsies. RESULTS: Paradoxically, TNBS colitis in CD39-null mice was characterized by improved survival, favorable clinical scores, and decreased MPO activity, when compared to wt mice (P <0.05). LPMC from TNBS colitis contained significantly increased amounts of T-cells (CD3(+) and CD4(+)) and TNF-alpha mRNA expression were increased over those in CD39 null mice (P <0.05). In contrast, oxazolone treated CD39-null and wt mice had comparable outcomes. In both ulcerative colitis and Crohn s disease, CD39 is present at high levels in intestinal tissue biopsies. CONCLUSIONS: TNBS colitis was attenuated in CD39-null mice whereas oxazolone-induced colitis was not impacted. Impaired adaptive cellular immune reactivity in the CD39-null environment appears protective in hapten-mediated Th1-type colitis. CD39 is expressed at high levels in clinical IBD tissues.",
author = "Kunzli, {Beat M} and Berberat, {Pascal O} and Dwyer, {Karen M} and Silvia Deaglio and Eva Csizmadia and Cowan, {Peter J} and D'Apice, {Anthony J F} and Moore, {Gregory Thomas Charles} and Keiichi Enjyoji and Helmut Friess and Robson, {Simon Christopher}",
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Kunzli, BM, Berberat, PO, Dwyer, KM, Deaglio, S, Csizmadia, E, Cowan, PJ, D'Apice, AJF, Moore, GTC, Enjyoji, K, Friess, H & Robson, SC 2011, 'Variable impact of CD39 in experimental murine colitis', Digestive Diseases and Sciences, vol. 56, no. 5, pp. 1393 - 1403. https://doi.org/10.1007/s10620-010-1425-9

Variable impact of CD39 in experimental murine colitis. / Kunzli, Beat M; Berberat, Pascal O; Dwyer, Karen M; Deaglio, Silvia; Csizmadia, Eva; Cowan, Peter J; D'Apice, Anthony J F; Moore, Gregory Thomas Charles; Enjyoji, Keiichi; Friess, Helmut; Robson, Simon Christopher.

In: Digestive Diseases and Sciences, Vol. 56, No. 5, 2011, p. 1393 - 1403.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Variable impact of CD39 in experimental murine colitis

AU - Kunzli, Beat M

AU - Berberat, Pascal O

AU - Dwyer, Karen M

AU - Deaglio, Silvia

AU - Csizmadia, Eva

AU - Cowan, Peter J

AU - D'Apice, Anthony J F

AU - Moore, Gregory Thomas Charles

AU - Enjyoji, Keiichi

AU - Friess, Helmut

AU - Robson, Simon Christopher

PY - 2011

Y1 - 2011

N2 - BACKGROUND: Dysregulation of immune responses in inflammatory bowel diseases (IBD) results in intestinal inflammation and vascular injury while exacerbating systemic disease. CD39 is an ectonucleotidase, expressed by T regulatory cells and dendritic cells, that hydrolyzes extracellular nucleotides to modify those cellular immune responses implicated in IBD. Genetic polymorphisms of CD39 have been linked to Crohn s disease while gene deletion in mice exacerbates dextran sodium sulphate-induced colitis. AIM: The aim of this study was to test how global deletion of CD39 in mice impacts other models of experimental colitis. METHODS: Colitis was induced in CD39-null and -wt mice, using trinitrobenzene sulfonic acid (TNBS, 125 mg/kg) administered intrarectally. Oxazolone colitis (1.5 oxazolone in 50 alcohol) was induced in comparable groups. Morphology, clinical and molecular parameters, and FACS analyses of lamina propria mononuclear cells (LPMC) were examined in CD39-null mice. CD39 expression was analyzed in human IBD biopsies. RESULTS: Paradoxically, TNBS colitis in CD39-null mice was characterized by improved survival, favorable clinical scores, and decreased MPO activity, when compared to wt mice (P <0.05). LPMC from TNBS colitis contained significantly increased amounts of T-cells (CD3(+) and CD4(+)) and TNF-alpha mRNA expression were increased over those in CD39 null mice (P <0.05). In contrast, oxazolone treated CD39-null and wt mice had comparable outcomes. In both ulcerative colitis and Crohn s disease, CD39 is present at high levels in intestinal tissue biopsies. CONCLUSIONS: TNBS colitis was attenuated in CD39-null mice whereas oxazolone-induced colitis was not impacted. Impaired adaptive cellular immune reactivity in the CD39-null environment appears protective in hapten-mediated Th1-type colitis. CD39 is expressed at high levels in clinical IBD tissues.

AB - BACKGROUND: Dysregulation of immune responses in inflammatory bowel diseases (IBD) results in intestinal inflammation and vascular injury while exacerbating systemic disease. CD39 is an ectonucleotidase, expressed by T regulatory cells and dendritic cells, that hydrolyzes extracellular nucleotides to modify those cellular immune responses implicated in IBD. Genetic polymorphisms of CD39 have been linked to Crohn s disease while gene deletion in mice exacerbates dextran sodium sulphate-induced colitis. AIM: The aim of this study was to test how global deletion of CD39 in mice impacts other models of experimental colitis. METHODS: Colitis was induced in CD39-null and -wt mice, using trinitrobenzene sulfonic acid (TNBS, 125 mg/kg) administered intrarectally. Oxazolone colitis (1.5 oxazolone in 50 alcohol) was induced in comparable groups. Morphology, clinical and molecular parameters, and FACS analyses of lamina propria mononuclear cells (LPMC) were examined in CD39-null mice. CD39 expression was analyzed in human IBD biopsies. RESULTS: Paradoxically, TNBS colitis in CD39-null mice was characterized by improved survival, favorable clinical scores, and decreased MPO activity, when compared to wt mice (P <0.05). LPMC from TNBS colitis contained significantly increased amounts of T-cells (CD3(+) and CD4(+)) and TNF-alpha mRNA expression were increased over those in CD39 null mice (P <0.05). In contrast, oxazolone treated CD39-null and wt mice had comparable outcomes. In both ulcerative colitis and Crohn s disease, CD39 is present at high levels in intestinal tissue biopsies. CONCLUSIONS: TNBS colitis was attenuated in CD39-null mice whereas oxazolone-induced colitis was not impacted. Impaired adaptive cellular immune reactivity in the CD39-null environment appears protective in hapten-mediated Th1-type colitis. CD39 is expressed at high levels in clinical IBD tissues.

U2 - 10.1007/s10620-010-1425-9

DO - 10.1007/s10620-010-1425-9

M3 - Article

VL - 56

SP - 1393

EP - 1403

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

SN - 0163-2116

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Kunzli BM, Berberat PO, Dwyer KM, Deaglio S, Csizmadia E, Cowan PJ et al. Variable impact of CD39 in experimental murine colitis. Digestive Diseases and Sciences. 2011;56(5):1393 - 1403. https://doi.org/10.1007/s10620-010-1425-9