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Modulating CD4+ T cell migration in the postischemic liver : hepatic stellate cells as new therapeutic target?Reifart, Jorg ...BACKGROUND: CD4+ T cells play a critical role during hepatic ischemia-reperfusion (I/R) injury although the mechanisms of their migration in the postischemic liver remain unclear. We answered the ... questions of whether hepatic stellate cells (HSCs) interact with CD4+ T cells during I/R of the liver and whether modulation of HSC activity affects T cell-dependent I/R injury. METHODS: In mice, migration of CD4+ T cells was analyzed in vivo using conventional intravital microscopy and two-photon microscopy. CD4+ T cell-HSC interactions were visualized after infusion of fluorescence-labeled CD4+ T cells into Cx3CR1 mice (mice exhibiting GFP-labeled HSCs) after I/R. Because the activation of HSC is controlled by endocannabinoid receptors, CB-1 and CB-2, the mice received treatment before I/R with the CB-2 agonist JWH-133 to reach HSC depletion or the CB-1 agonist arachidonylcyclopropylamide to activate HSCs. Sinusoidal perfusion and liver transaminases were used as markers of I/R injury. RESULTS: Hepatic I/R induced CD4+ T cell recruitment in sinusoids. More than 25% of adherent CD4+ T cells were colocalized with HSCs during reperfusion, suggesting a direct cell-cell interaction. The HSC deactivation with JWH-133 significantly attenuated the CD4+ T cell recruitment in the postischemic liver and reduced I/R injury as compared to the vehicle-treated group. The HSC hyperactivation by CB-1, however, did not affect T-cell migration and even increased perfusion failure. CONCLUSION: Our in vivo data suggest that CD4+ T cells interact with HSCs on their migration into the hepatic parenchyma, and a depletion or deactivation of HSCs protects the liver from T cell-dependent I/R injury.Source: Transplantation. - ISSN 0041-1337 (Vol. 99, no. 1, jan. 2015, str. 41-47)Type of material - article, component partPublish date - 2015Language - englishCOBISS.SI-ID - 81792001
Author
Reifart, Jorg |
Rentsch, Markus |
Coletti, Raffaele |
Sobočan, Monika |
Thasler, Wolfgang |
Khandoga, Andrej
Topics
nefrologija |
bolezni ledvic |
hepatitis
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Reifart, Jorg | |
Rentsch, Markus | |
Coletti, Raffaele | |
Sobočan, Monika | 50187 |
Thasler, Wolfgang | |
Khandoga, Andrej |
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