B lymphocytes limit senescence-driven fibrosis resolution and favor hepatocarcinogenesis in mouse liver injury

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Francesca FaggioliBarbara Cassani

Abstract

Hepatocellular carcinoma (HCC) is a frequent neoplasia and a leading cause of inflammation-related cancer mortality. Despite that most HCCs arise from persistent inflammatory conditions, pathways linking chronic inflammation to cancer development are still incompletely elucidated. We dissected the role of adaptive immunity in the Mdr2 knockout (Mdr2-/- ) mouse, a model of inflammation-associated cancer, in which ablation of adaptive immunity has been induced genetically (Rag2-/- Mdr2-/- and μMt-Mdr2-/- mice) or with in vivo treatments using lymphocyte-specific depleting antibodies (anti-CD20 or anti-CD4/CD8). We found that activated B and T lymphocytes, secreting fibrogenic tumor necrosis factor alpha (TNFα) and other proinflammatory cytokines, infiltrated liver of the Mdr2-/- mice during chronic fibrosing cholangitis. Lymphocyte ablation, in the Rag2-/- Mdr2-/- and μMt-Mdr2-/- mice, strongly suppressed hepatic stellate cell (HSC) activation and extracellular matrix deposition, enhancing HSC transition to cellular senescence. Moreover, lack of lymphocytes changed the intrahepatic metabolic/oxidative state, resulting in skewed macrophage polarization toward an anti-inflammatory M2 phenotype. Remarkably, hepatocarcinogenesis was ...Continue Reading

References

Jul 1, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J MurakamiA Watanabe
May 9, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A J GrantD H Adams
Jul 4, 2002·Annals of the New York Academy of Sciences·Giuseppe MontaltoLuigi A M Castagnetta
Mar 22, 2003·The Journal of Investigative Dermatology·Shinichi SatoKazuhiko Takehara
Aug 27, 2004·Nature·Eli PikarskyYinon Ben-Neriah
Feb 4, 2005·The Journal of Clinical Investigation·Ramón Bataller, David A Brenner
May 17, 2005·Cancer Cell·Karin E de VisserLisa M Coussens
Oct 7, 2005·Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition·Joyce K StechmillerLinda Cowan
Nov 9, 2005·The Journal of Clinical Investigation·Tatiana I NovobrantsevaAlexander Ibraghimov
Oct 24, 2007·Nature Medicine·Ekihiro SekiRobert F Schwabe
Jul 17, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hila BarashRinat Abramovitch
Aug 30, 2008·Cell·Valery KrizhanovskyScott W Lowe
Oct 6, 2009·Cancer Cell·Johannes HaybaeckMathias Heikenwalder
Feb 9, 2010·Cancer Cell·Pauline AndreuLisa M Coussens
Sep 23, 2010·Journal of the National Cancer Institute·Jonathan A EwaldDavid F Jarrard
Aug 2, 2011·Cellular and Molecular Life Sciences : CMLS·Lester F Lau
Feb 23, 2012·Lancet·Alejandro FornerJordi Bruix
Aug 25, 2012·World Journal of Gastroenterology : WJG·Hayato Nakagawa, Shin Maeda
Nov 13, 2012·Annual Review of Physiology·Judith Campisi
Feb 5, 2013·Nature·Heidi BraumüllerMartin Röcken
Aug 16, 2013·Current Pharmaceutical Design·Myoung-Kuk JangYoung-Hwa Chung
Oct 10, 2013·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Harald SchremMoritz Kleine
Oct 12, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Antonio SicaAlberto Mantovani
Feb 25, 2014·Journal of Hepatology·Peter FickertUNKNOWN International PSC Study Group (IPSCSG)
Apr 10, 2014·Disease Models & Mechanisms·Matthew Giannandrea, William C Parks
Jun 21, 2014·Nature Reviews. Immunology·Costantino PitzalisSimon A Jones
Sep 24, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Abhijeet Kumar, Dung T Le
Oct 21, 2015·Nature Reviews. Gastroenterology & Hepatology·Jesús PrietoBruno Sangro
Jun 7, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yannan FanFlavio Maina

❮ Previous
Next ❯

Citations

Feb 11, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tim F Greten
Apr 26, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Manoj ThapaArash Grakoui
Mar 5, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Adiba I AzadGregory J Gores
Jun 3, 2020·Nature Reviews. Gastroenterology & Hepatology·Prakash RamachandranNeil C Henderson
Aug 10, 2020·Experimental & Molecular Medicine·Seo-Young KooChang-Woo Lee
Feb 25, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Katelynn Madill-ThomsenPhilip F Halloran
Apr 9, 2020·Cells·Natascha RoehlenThomas F Baumert
Apr 6, 2021·Frontiers in Immunology·Julie GiraudMaya Saleh
May 12, 2021·Hepatobiliary & Pancreatic Diseases International : HBPD INT·Hao LiYing-Zi Ming
May 8, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fanta BarrowXavier S Revelo
Jul 9, 2021·Frontiers in Oncology·Miaomiao QinXiongxiong Pan
Aug 11, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yuanyuan ZhengChuanyong Guo
Aug 25, 2021·International Immunopharmacology·Fangming YangZhun Xiao
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Jing YangXing Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Related Papers

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Matthias BartneckFrank Tacke
Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Reina SasakiRatna B Ray
The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology
Bin-Bin WangHuijie Bian
© 2022 Meta ULC. All rights reserved