Posttransplant Hemophagocytic Lymphohistiocytosis Driven by Myeloid Cytokines and Vicious Cycles of T-Cell and Macrophage Activation in Humanized Mice

Frontiers in Immunology
Satoshi YoshiharaYong-Guang Yang

Abstract

Hemophagocytic lymphohistiocytosis (HLH) has recently been increasingly reported as an important complication after stem cell transplantation, in line with the increase in the number of HLA-mismatched transplantation. Although previous clinical studies have shown an elevation of inflammatory cytokines in patients with HLH after hematopoietic stem cell transplantation, as well as those after viral infection or autoimmune disease, the disease pathogenesis remains poorly understood. Here we explored this issue in humanized mice with functional human lymphohematopoietic systems, which were constructed by transplantation of human CD34+ cells alone, or along with human fetal thymus into NOD/SCID/γc-/- (NSG) or NSG mice carrying human SCF/GM-CSF/IL-3 transgenes (SGM3). In comparison with humanized NSG (huNSG) mice, huSGM3 mice had higher human myeloid reconstitution and aggressive expansion of human CD4+ memory T cells, particularly in the absence of human thymus. Although all huNSG mice appeared healthy throughout the observation period of over 20 weeks, huSGM3 mice developed fatal disease characterized by severe human T cell and macrophage infiltrations to systemic organs. HuSGM3 mice also showed severe anemia and thrombocytopenia w...Continue Reading

References

Nov 8, 2003·International Journal of Hematology·James L M FerraraTakanori Teshima
Jun 28, 2008·Blood·Siegfried Kohler, Andreas Thiel
Mar 3, 2009·International Journal of Hematology·Abderrahman AbdelkefiTarek Ben Othman
Aug 28, 2009·British Journal of Haematology·Shinsuke TakagiShuichi Taniguchi
Dec 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Qingfeng ChenJianzhu Chen
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takashi OnoeMegan Sykes
Mar 17, 2012·Science Translational Medicine·Hannes KalscheuerMegan Sykes
Oct 13, 2012·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Jan 22, 2013·Annual Review of Immunology·Anthony RongvauxMarkus G Manz
Apr 17, 2013·The Journal of Rheumatology·Raffaele StrippoliFabrizio De Benedetti
Nov 5, 2013·The American Journal of Pathology·Annemarie E van NieuwenhuijzeIan P Wicks
Mar 19, 2014·Nature Biotechnology·Anthony RongvauxRichard A Flavell
May 6, 2014·Blood Reviews·Gritta E Janka, Kai Lehmberg
Jun 27, 2014·Journal of Blood Medicine·Melissa R George
Dec 2, 2015·International Journal of Hematology·Sarita Rani JaiswalSuparno Chakrabarti

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Citations

Jun 30, 2019·Transplant Infectious Disease : an Official Journal of the Transplantation Society·Sarita Rani JaiswalSuparno Chakrabarti
Sep 10, 2020·Veterinary Pathology·Sandra BlümichGiovanni Pellegrini
Jun 7, 2019·International Journal of Molecular Sciences·Ryoji ItoSatoshi Nunomura
Oct 13, 2020·Frontiers in Oncology·Huimin TianZheng Hu
Jan 21, 2021·Veterinary Pathology·Hibret A Adissu
Oct 27, 2020·Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion·Akanksha GargSonia Parikh
Nov 3, 2020·Frontiers in Immunology·Liguang SunYong-Guang Yang
Feb 22, 2021·Journal of Autoimmunity·Mohsen Khosravi-MaharlooeiMegan Sykes
May 20, 2020·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Sarita Rani JaiswalSuparno Chakrabarti
Dec 14, 2021·Molecular Metabolism·Mohsen Khosravi-MaharlooeiRemi J Creusot

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Methods Mentioned

BETA
transgenic
X-ray
density gradient centrifugation
flow cytometry
density

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