Éditeur(s) : HAL CCSD Impact journals
Résumé : International audience
Interleukin (IL)-33 has been recently reported to be strongly pro-fibrogenic in various models of liver disease. Our aim was to study the role of endogenous IL-33 in a diet-induced model of steatohepatitis. IL-33 deficient mice and wild type (WT) littermates received a high-fat diet (HFD), or a standard diet for 12 weeks. The HFD-induced steatohepatitis was associated with an upregulation of IL-33 transcripts and protein. An insulin tolerance test revealed lower systemic insulin sensitivity in IL33-/-HFD mice than in WT-HFD mice. Nevertheless, IL-33 deficiency did not affect the severity of liver inflammation by histological and transcriptomic analyses, nor the quantity of liver fibrosis. Livers from HFD mice had more myeloid populations, markedly fewer NKT cells and higher proportion of ST2+ Treg cells and ST2+ type 2 innate lymphoid cells (ILC2), all unaffected by IL-33 deficiency. In conclusion, deficiency of endogenous IL-33 does not affect the evolution of experimental diet-induced steatohepatitis towards liver fibrosis.
ISSN: 1949-2553

hal-01578584
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578584
DOI : 10.18632/oncotarget.18335
PUBMED : 28611297

Éditeur(s) : HAL CCSD Cambridge University Press (CUP)
Résumé : We present detailed biostratigraphy based on conodonts and palaeoenvironmental trends deduced from microfacies and conodont abundance through the Famennian (Late Devonian) at Col des Tribes (Montagne Noire, France). The succession is characterized by micritic limestones deposited in settings oscillating between mid to outer ramp. Facies contain poor fauna, widely dominated by nektonic organisms. This section is complete and one of the most conodont-rich for the Famennian of the north Gondwana-related area. The Upper Kellwasser event (Frasnian–Famennian boundary) and the Hangenberg (Devonian–Carboniferous boundary) have been lithologically identified. They are characterized by decimetre-thick black dysoxic to anoxic argillaceous sediments. The Condroz and annulata events, although not materialized by lithological changes, have been positioned due to the precise stratigraphy. The first event occurred during the deposition of condensed ferruginous facies (griotte limestones) and the second event during the deposition of micrites barren of benthic fauna. The combination of information from both facies and conodont biofacies changes allows a general sea-level curve through the entire Famennian for north Gondwana to be proposed for the first time. At Col des Tribes, the general trend is a slight deepening upwards from triangularis to trachytera zones, then a pronounced shallowing-upwards trend from upper trachytera to praesulcata zones. This curve correlates with the well-known reference curve from Euramerica concerning the late Famennian (trachytera to praesulcata Zones). There are some discrepancies in minor cycles which can be explained by tectonical phenomena at the onset of the edification of the Variscan belt in Europe.
ISSN: 0016-7568

hal-01115222
https://hal.archives-ouvertes.fr/hal-01115222
DOI : 10.1017/S0016756813000927

Éditeur(s) : HAL CCSD Borntraeger Science Publishers
Résumé : This study characterizes the stratigraphical context as well as the palaeoenvironmental and sealevel trends during the Late Frasnian and Famennian in the Buschteich section (Thuringia, Germany). An integrated approach combines conodont biostratigraphy, chemostratigraphy based on carbon and oxygen isotopes, conodont biofacies analyses and investigations of the morphotypes of foraminifera that occur in the section was applied. Conodonts provided a fine-scale biostratigraphical framework. All the Famennian conodont biozones were identified, with the exception of the three lowest. The Frasnian – Famennian transition was further identified by a positive carbon isotope excursion. This continuous Famennian record is developed in a condensed limestone succession. The reddish Griotte facies, typical of strata of this period, were not documented. Black shales were not developed except for an interval of dark colored mud rocks corresponding to the Hangenberg event at the top of the section. The carbonate succession of Buschteich was deposited in an outer ramp environment, pelagic organisms are the dominant fauna. This is corroborated by the overall dominance of the deep-water conodont genus Palmatolepis. Microfacies, conodont biofacies and foramini fera indicated a deepening trend from the Lower crepida to the Lower rhomboidea Zone, followed by a shallowing trend from the Upper rhomboidea to the praesulcata Zone. This sequence overall matches the sea level reference curve for Euramerica. The timing of maximum water depth at Buschteich, as well as the general sea-level reference record, differs from the Col des Tribes (Montagne Noire, France). Differential uplift or overprinting of the long-term eustatic changes may be the cause of the discrepancy in the local sea-level records.
ISSN: 0078-0421

hal-01623111
https://hal.archives-ouvertes.fr/hal-01623111
DOI : 10.1127/nos/2016/0318

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : International audience
The IL-33/ST2 axis plays a protective role in T-cell-mediated hepatitis, but little is known about the functional impact of endogenous IL-33 on liver immunopathology. We used IL-33-deficient mice to investigate the functional effect of endogenous IL-33 in concanavalin A (Con A)-hepatitis. IL-33(-/-) mice displayed more severe Con A liver injury than wild-type (WT) mice, consistent with a hepatoprotective effect of IL-33. The more severe hepatic injury in IL-33(-/-) mice was associated with significantly higher levels of TNF-alpha and IL-1 beta and a larger number of NK cells infiltrating the liver. The expression of Th2 cytokines (IL-4, IL-10) and IL-17 was not significantly varied between WT and IL-33(-/-) mice following Con A-hepatitis. The percentage of CD25(+) NK cells was significantly higher in the livers of IL-33(-/-) mice than in WT mice in association with upregulated expression of CXCR3 in the liver. Regulatory T cells (Treg cells) strongly infiltrated the liver in both WT and IL-33(-/-) mice, but Con A treatment increased their membrane expression of ST2 and CD25 only in WT mice. In vitro, IL-33 had a significant survival effect, increasing the total number of splenocytes, including B cells, CD4(+) and CD8(+) T cells, and the frequency of ST2(+) Treg cells. In conclusion, IL-33 acts as a potent immune modulator protecting the liver through activation of ST2(+) Treg cells and control of NK cells.
ISSN: 0193-1857

hal-01366372
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366372
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366372/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366372/file/Ablation%20of%20interaction%20between%20IL-33%20and%201%20ST2.pdf
DOI : 10.1152/ajpgi.00097.2016

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
UNLABELLED: Interleukin (IL)-33, a member of the IL-1 cytokine family, positively correlates with acute hepatitis and chronic liver failure in mice and humans. IL-33 is expressed in hepatocytes and is regulated by natural killer T (NKT) cells during concanavalin A (ConA)-induced acute liver injury. Here, we investigated the molecular mechanisms underlying the expression of IL-33 during acute hepatitis. The expression of IL-33 and its regulation by death receptor pathways was investigated after the induction of ConA-acute hepatitis in wildtype (WT), perforin(-/-) , tumor necrosis factor related apoptosis inducing ligand (TRAIL)(-/-) , and NKT cell-deficient (CD1d(-/-) ) mice. In addition, we used a model of acute liver injury by administering Jo2/Fas-antibody or D-galactosamine-tumor necrosis factor alpha (TNFα) in WT mice. Finally, the effect of TRAIL on IL-33 expression was assessed in primary cultured murine hepatocytes. We show that IL-33 expression in hepatocytes is partially controlled by perforin during acute liver injury, but not by TNFα or Fas ligand (FasL). Interestingly, the expression of IL-33 in hepatocytes is blocked during ConA-acute hepatitis in TRAIL-deficient mice compared to WT mice. In contrast, administration of recombinant murine TRAIL associated with ConA-priming in CD1d-deficient mice or in vitro stimulation of murine hepatocytes by TRAIL but not by TNFα or Jo2 induced IL-33 expression in hepatocytes. The IL-33-deficient mice exhibited more severe ConA liver injury than WT controls, suggesting a protective effect of IL-33 in ConA-hepatitis. CONCLUSION: The expression of IL-33 during acute hepatitis is dependent on TRAIL, but not on FasL or TNFα.
ISSN: 0270-9139

hal-00874194
https://hal.archives-ouvertes.fr/hal-00874194
PUBMED : 22961755
DOI : 10.1002/hep.25893

Éditeur(s) : HAL CCSD Cambridge University Press (CUP)
Résumé : International audience
The Ben Zireg anticline NW of Bechar yields the currently most-important Frasnian succession on the northern margin of the Algerian Sahara. It represents 26.5 m of calcilutites which are attributed to the middle–late Frasnian. As the early Frasnian is not represented, the succession rests conformably on undifferentiated, probably late Givetian, substrate. Fine-scaled conodont biostratigraphy reveals a continuous sequence of Montagne Noire Zones 5–13, superseded by the earliest Famennian Lower triangularis Zone. The deposits are organized into 15 sedimentary cycles that are initially condensed and become dilated upwards. Conodont biofacies indicate an overall deepening towards the top of the section with an episode of slight shallowing at the MN11/12 transition marked by an increase of ancyrodellids, which is also seen in the Marhouma section of the Ougarta region (SW Algeria). Homogeneous calcareous microfacies with only a few shaly intercalations determine a predominantly oxygenated depositional environment on an outer platform, submarine rise or ramp setting. This is also indicated by relatively low sedimentation rates which are similar in selected sections from the Tafilalt platform, and contrast with those from the Marhouma trough and the Maider basin. Unlike other Frasnian successions south of the Atlas Fault, but similar to the Moroccan Meseta, the Upper Kellwasser horizon is clearly discriminated at Ben Zireg by an outstanding occurrence of black shales on top of the oxygenated latest Frasnian deposits.
ISSN: 0016-7568

hal-01217151
https://hal.archives-ouvertes.fr/hal-01217151
DOI : 10.1017/S0016756814000715

Éditeur(s) : HAL CCSD
Résumé : International audience
The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.
Mediators of Inflammation

hal-01544268
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01544268
DOI : 10.1155/2017/1359064
PUBMED : 28607531
PUBMEDCENTRAL : PMC5457781