Human CD200 suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis

Sakai, Rieko; Maeda, Akira; Choi, Thuy-Vy; Lo, Pei‐Chi; Jiaravuthisan, Patmika; Shabri, Afifah Mod; Wang, Han-Tang; Matsuura, Ryohei; Kodama, Tatsuhiko; Eguchi, Hiroshi; Okuyama, Hiroomi; Miyagawa, Shuji

doi:10.1007/s00595-017-1546-2

Cited by 23 publications

(15 citation statements)

References 33 publications

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“…In animal models, CD200/CD200R signaling prevents allograft rejection. [36] Yu et al [5] showed that CD200R positively stimulated DCs, modulated alloimmune tolerance, and reduced natural killer cell activity in transgenic mice overexpressing CD200. Moreover, enhanced interleukin 10 and TGF-β production through CD200R increased the chance of graft acceptance.…”

Section: Discussionmentioning

confidence: 99%

Pre-transplant CD200 and CD200R1 concentrations are associated with post-transplant events in kidney transplant recipients

Oweira¹,

Khajeh²,

Mohammadi³

et al. 2019

Medicine

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CD200 is an immunoglobulin superfamily membrane protein that binds to a myeloid cell-specific receptor and induces inhibitory signaling. The aim of this study was to investigate the role of CD200 and its receptor (CD200R1) on kidney transplant (KTx) outcome. In a collective of 125 kidney recipients (University hospital, Heidelberg, Germany), CD200 and CD200R1 concentrations were evaluated immediately before transplantation. Recipient baseline and clinical characteristics and KTx outcome, including acute rejection (AR), acute tubular necrosis, delayed graft function, cytomegalovirus (CMV) and human polyomaviridae (BK) virus infections, and graft loss were evaluated during the first post-transplant year. The association of CD200 and CD200R1 concentrations and CD200R1/CD200 ratios with the outcome of KTx was investigated for the first time in a clinical setting in a prospective cohort. There was a positive association between pre-transplant CD200R1 concentrations and CMV (re)activation (P = .041). Also, increased CD200R1 concentration was associated with a longer duration of CMV infection (P = .049). Both the frequency of AR and levels of creatinine (3 and 6 months after KTx) were significantly higher in patients with an increased CD200R1/CD200 ratio (median: 126 vs 78, P = .008). Increased pre-transplant CD200R1/CD200 ratios predict immunocompetence and risk of AR, whereas high CD200R1 concentrations predict immunosuppression and high risk of severe CMV (re)activation after KTx.

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Section: Discussionmentioning

confidence: 99%

Pre-transplant CD200 and CD200R1 concentrations are associated with post-transplant events in kidney transplant recipients

Oweira¹,

Khajeh²,

Mohammadi³

et al. 2019

Medicine

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“…Various factors are related to macrophage activation: for example, activation by innate antibodies (Fcγ activation), IFN‐γ (by NK and Th1), and complement pathway (antibody‐independent pathway among the classical pathways, second pathway, and lectin pathway), and danger‐associated molecular pattern (DAMP)‐induced activation 17 . Among these, antibody‐independent complement pathway or DAMP‐induced macrophage activation is T/B/NK cell‐independent factors.…”

Section: Discussionmentioning

confidence: 99%

The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats

Furuya

Zheng

et al. 2021

Xenotransplantation

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Background The human‐to‐rat hematopoietic stem cell transplantation (HSCT) model is rare, unlike its human‐to‐mouse counterpart. The rat models are desired, especially in areas of physiology, toxicology, and pharmacology. In addition to lymphocytes, macrophages are also considered to be important for xenotransplantation. We generated a rat xenotransplantation model to prove the role of macrophages as a xenotransplantation barrier. Methods Immunodeficiency in SRG rats, which are Sprague–Dawley (SD) rats lacking Rag2 and Il2rg, was confirmed by flow cytometry and spleen immunostaining. Human umbilical cord blood was collected after scheduled cesarean section at the University of Tsukuba Hospital. Cord blood mononuclear cells (CB‐MNCs) were transplanted into the SRG rats administered several injections of clodronate liposome (CL), which cause macrophage depletion. Survival of human cells was observed by flow cytometry. Rat macrophage phagocytosis assay was performed to check the species‐specific effects of rat macrophages on injected human/rat blood cells. Results SRG rats were deficient in T/B/NK cells. Without CL pretreatment, human CB‐MNCs were removed from SRG rats within 7 hours after transplantation. The rats pretreated with CL could survive after transplantation. Prolonged survival for more than 4 weeks was observed only following a one‐time CL injection. Rat macrophages had a species‐specific potential for the phagocytosis of human blood cells in vivo. Conclusion In human‐to‐rat HSCT, the short period of early macrophage control, leading to macrophage immunotolerance, is important for engraftment. The generated model can be useful for the creation of future xenotransplantation models or other clinical research.

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“…CD200 (OX-2 membrane glycoprotein) is a transmembrane protein that is typically expressed on the surface of hematopoietic-derived cells, as well as B-cells, activated T cells, endothelial cells and neuronal cells ( 262 ). Expression of CD200 on endothelial cells was found to inhibit phagocytosis of those cells by macrophages, possibly by engaging the CD200 receptor, CD200R ( 263 ). However, CD200 inhibits inflammation via CD200R ( 262 ), so it is possible that the inhibition of phagocytosis is indirect via inhibiting inflammation.…”

Section: The Phagocytic Codementioning

confidence: 99%

The Phagocytic Code Regulating Phagocytosis of Mammalian Cells

et al. 2021

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Mammalian phagocytes can phagocytose (i.e. eat) other mammalian cells in the body if they display certain signals, and this phagocytosis plays fundamental roles in development, cell turnover, tissue homeostasis and disease prevention. To phagocytose the correct cells, phagocytes must discriminate which cells to eat using a ‘phagocytic code’ - a set of over 50 known phagocytic signals determining whether a cell is eaten or not - comprising find-me signals, eat-me signals, don’t-eat-me signals and opsonins. Most opsonins require binding to eat-me signals – for example, the opsonins galectin-3, calreticulin and C1q bind asialoglycan eat-me signals on target cells - to induce phagocytosis. Some proteins act as ‘self-opsonins’, while others are ‘negative opsonins’ or ‘phagocyte suppressants’, inhibiting phagocytosis. We review known phagocytic signals here, both established and novel, and how they integrate to regulate phagocytosis of several mammalian targets - including excess cells in development, senescent and aged cells, infected cells, cancer cells, dead or dying cells, cell debris and neuronal synapses. Understanding the phagocytic code, and how it goes wrong, may enable novel therapies for multiple pathologies with too much or too little phagocytosis, such as: infectious disease, cancer, neurodegeneration, psychiatric disease, cardiovascular disease, ageing and auto-immune disease.

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Human CD200 suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis

Abstract: Our findings indicate that human CD200 suppresses the xenogeneic rejection by CD200R macrophages and that the generation of hCD200 transgenic pigs for use in xenografts is very attractive for preventing the macrophage-mediated rejection.

Cited by 23 publications

References 33 publications

Pre-transplant CD200 and CD200R1 concentrations are associated with post-transplant events in kidney transplant recipients

Pre-transplant CD200 and CD200R1 concentrations are associated with post-transplant events in kidney transplant recipients

The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats

The Phagocytic Code Regulating Phagocytosis of Mammalian Cells

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