Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling-dependent CD8 T-cell activation

Department of Cellular Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Blood (Impact Factor: 9.78). 05/2009; 113(23):5819-28. DOI: 10.1182/blood-2008-11-190033
Source: PubMed

ABSTRACT Class A scavenger receptor (SRA), also known as CD204, has been shown to participate in the pathogenesis of atherosclerosis and the pattern recognition of pathogen infection. However, its role in adaptive immune responses has not been well defined. In this study, we report that the lack of SRA/CD204 promotes Toll-like receptor (TLR)4 agonist-augmented tumor-protective immunity, which is associated with enhanced activation of CD8(+) effector T cell and improved inhibition of tumor growth. Dendritic cells (DCs) deficient in SRA/CD204 display more effective immunostimulatory activities upon TLR4 engagement than those from wild-type counterparts. Silencing of SRA/CD204 by RNA interference improves the ability of DCs to prime antigen-specific CD8(+) T cells, suggesting that antigen-presenting cells, for example, DCs, play a major role in SRA/CD204-mediated immune modulation. Our findings reveal a previously unrecognized role for SRA/CD204, a non-TLR pattern recognition receptor, as a physiologic negative regulator of TLR4-mediated immune consequences, which has important clinical implications for development of TLR-targeted immunotherapeutic intervention.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The induction of donor-specific tolerance to transplanted cells and organs, while preserving immune function as a whole, remains a highly sought after and elusive strategy for overcoming transplant rejection. Tolerance necessitates modulating a diverse array of cell types that recognize and respond to alloantigens, including antigen presenting cells and T lymphocytes. Nanotherapeutic strategies that employ cellular and biomaterial engineering represent an emerging technology geared towards the goal of inducing transplant tolerance. Nanocarriers offer a platform for delivering antigens of interest to specific cell types in order to achieve tolerogenic antigen presentation. Furthermore, the technologies also provide an opportunity for local immunomodulation at the graft site. Nanocarriers delivering a combination of antigens and immunomodulating agents, such as rapamycin, provide a unique technology platform with the potential to enhance outcomes for the induction of transplant tolerance. Copyright © 2015. Published by Elsevier Inc.
    Clinical Immunology 03/2015; DOI:10.1016/j.clim.2015.03.013 · 3.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this review, we discuss an immunological-driven sign termed the Completed Self, which is related to a holistic determination of health vs. disease. This sign (human plus commensal microbiota) forms the human superorganism. The worldwide emergence of an epidemic of chronic diseases has caused increased healthcare costs, increased premature mortality and reduced quality of life for a majority of the world's population. In addition, it has raised questions concerning the interactions between humans and their environment and potential imbalances. Misregulated inflammation, a host defense-homeostasis disorder, appears to be a key biomarker connecting a majority of chronic diseases. We consider the apparent contributors to this disorder that promote a web of interlinked comorbid conditions. Three key events are suggested to play a role: (1) altered epigenetic programming (AEP) that may span multiple generations, (2) developmental immunotoxicity (DIT), and (3) failure to adequately incorporate commensal microbes as a newborn (i.e., the incomplete self). We discuss how these three events can combine to determine whether the human superorganism is able to adequately and completely form during early childhood. We also discuss how corruption of this event can affect the risk of later-life diseases.
    Entropy 12/2012; 14(11):2036-2065. DOI:10.3390/e14112036 · 1.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microglia mediated neuroinflammation plays a crucial role in intracerebral hemorrhage (ICH). Therefore, the negative feedback immune mechanism to keep microglia homeostasis and inhibit the related inflammatory injury is important. Scavenger receptor A (SRA), a pattern recognition molecule, is a physiologic negative regulator of immune consequences. However, its role in microglia mediated immune response has not been well defined. In this study, we detected SRA expression and inflammatory response of microglia treated with erythrocyte lysate in vitro, and observed the cerebral water content and neurological deficit of ICH mice in vivo. We found that SRA was highly expressed in erythrocyte lysate treated microglia. Interestingly, genetic SRA ablation increased microglia activation and cytokine production, and sensitized mice to ICH induced neuron injury. In addition, we adoptive transferred microglia (WT) into ICH mice (SRA-/-), and found that the ICH-induced inflammation injury was effectively ameliorated. Therefore, the results demonstrated that SRA could attenuate microglia mediated inflammation injury in ICH. In addition, SRA mediated negative feedback mechanism in neuroimmune homeostasis might provide a novel therapeutical strategy for ICH. Scavenger receptor SRA restrains T cell activation and protects against concanavalin A-induced hepatic injury. Copyright © 2014. Published by Elsevier B.V.
    Journal of Neuroimmunology 11/2014; 278. DOI:10.1016/j.jneuroim.2014.11.010 · 2.79 Impact Factor