Complement regulatory protein Crry/p65 costimulation expands natural treg cells with enhanced suppressive properties in proteoglycan-induced arthritis.

  title={Complement regulatory protein Crry/p65 costimulation expands natural treg cells with enhanced suppressive properties in proteoglycan-induced arthritis.},
  author={G. Ojeda and E. Pini and C. Eguiluz and M. Montes-Casado and F. Broere and W. van Eden and J. Rojo and P. Portol{\'e}s},
  journal={Arthritis and rheumatism},
  volume={63 6},
OBJECTIVE To investigate the costimulatory role of Crry/p65 (Crry), a membrane complement regulatory protein, on the expansion and function of natural Treg cells and their ability to ameliorate proteoglycan-induced arthritis (PGIA), an animal model of inflammatory arthritis in which the role of natural Treg cells is not well established. METHODS CD4+CD25+ natural Treg cells from BALB/c mice were activated in vitro and costimulated by Crry. The expanded cells were phenotypically characterized… Expand
Impaired intestinal tolerance in the absence of a functional complement system.
It is shown in C3-deficient mice and human patients that intestinal tolerance fails in the absence of functional complement, and complement is identified as an important and nonredundant regulator of intestinal tolerance. Expand
Changes of CD4+ CD25+ Regulatory T Cells, FoxP3 in Adjuvant Arthritis Rats with Damage of Pulmonary Function and Effects of Tripterygium Glycosides Tablet
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It is suggested that extrauterine adipsin hematogenously reaches the placenta, activates complement C3, and promotes destruction of the feto-maternal barrier in aborted implantation sites and may be a crucial cause of spontaneous abortion. Expand
CD4+ CD25− FoxP3+ regulatory cells are the predominant responding regulatory T cells after human rotavirus infection or vaccination in gnotobiotic pigs
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Antigen‐specific in vitro expansion of factor VIII‐specific regulatory T cells induces tolerance in hemophilia A mice
  • Bryn M. Smith, Meghan J. Lyle, Alex C. Chen, C. Miao
  • Medicine
  • Journal of thrombosis and haemostasis : JTH
  • 2019
Following protein replacement therapy, one‐third of severe hemophilia A patients develop antibodies to factor VIII (FVIII), which also hinders the efficacy of gene therapy. Regulatory T cells (Tregs)Expand
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Markers of tolerance development to food allergens
There is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy. Expand
A Complement to T Cell Immunity


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Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells
In this study we demonstrate a new form of immunoregulation: engagement on CD4+ T cells of the complement regulator CD46 promoted the effector potential of T helper type 1 cells (TH1 cells), but asExpand
Mechanisms of foxp3+ T regulatory cell-mediated suppression.
The in vitro model systems that have been developed to define the mechanisms used by Treg cells to suppress a large number of distinct target cell types are reviewed. Expand
CD4+CD25+ immunoregulatory T cells may not be involved in controlling autoimmune arthritis
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Crry/p65, a Membrane Complement Regulatory Protein, Has Costimulatory Properties on Mouse T Cells1
Analysis of intracellular intermediaries shows that Crry/p65-CD3 coligation enhances certain TCR/CD3-mediated signals, producing increased early tyrosine phosphorylation of many substrates and enhanced activation of the mitogen-activated protein kinase, extracellular signal-related kinase. Expand
Mouse CD4+ CD25+ T regulatory cells are protected from autologous complement mediated injury by Crry and CD59.
It is shown that at least in mice, CD4(+)CD25(+)foxp3(+) Treg cells are not homogenous and could be further divided into subgroups based on CD59 expression, and that both Crry and CD59 are required to protect T Reg cells from autologous complement mediated injury. Expand
Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype
It is shown that co-engagement of CD3 and the complement regulator CD46 in the presence of IL-2 induces a Tr1-specific cytokine phenotype in human CD4+ T cells, suggesting that the complement system has a previously unappreciated role in T-cell-mediated immunity and tolerance. Expand
Complement drives Th17 cell differentiation and triggers autoimmune arthritis
The data suggest that complement activation by exogenous or endogenous stimulation can initiate Th17 cell differentiation and expansion in certain autoimmune diseases and presumably in microbial infections. Expand
Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses.
  • S. Sakaguchi
  • Biology, Medicine
  • Annual review of immunology
  • 2004
How naturally arising CD25+CD4+ regulatory T cells contribute to the maintenance of immunologic self-tolerance and negative control of various immune responses, and how they can be exploited to prevent and treat autoimmune disease, allergy, cancer, and chronic infection, or establish donor-specific transplantation tolerance are discussed. Expand
Autologous bone marrow transplantation in autoimmune arthritis restores immune homeostasis through CD4+CD25+Foxp3+ regulatory T cells.
It is shown that regulatory T cells (Tregs) play a role in the natural disease course of proteoglycan-induced arthritis (PGIA) and in disease remission by aBMT and can open the way to explore therapeutic interventions to further improve treatment of AID and disease relapses. Expand