CD200/CD200R Paired Potent Inhibitory Molecules Regulating Immune and Inflammatory Responses; Part II : CD 200/CD200R Potential Clinical Applications

Holmannová, Drahomíra; Koláčková, Martina; Kondělková, Kateřina; Kuneš, P; Krejsek, Jan; Ctirad, Andrjos

doi:10.14712/18059694.2015.56

Cited by 17 publications

(15 citation statements)

References 49 publications

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“…These two publications were landmark studies establishing the significance of CD200 and CD200R interactions as key regulators of inflammation in the brain. Since then, the field has grown significantly and has become specialized in studying the role of CD200 in a number of peripheral cell-mediated inflammatory and immune conditions, including arthritis 27,28], transplantation [29], viral infections [30,31], in the field of cancer [32,33] and also as a feature of neuroinflammation. CD200 is now known to be a significant player in cancer metastasis, with upregulation of CD200 being a negative factor as it promotes the evasion of cancer cells, including cancer stem cells, from the innate immune system [34].…”

Section: Biology Of Cd200 and The Cd200rmentioning

confidence: 99%

Understanding the Neurobiology of Cd200 and the Cd200 Receptor: A Therapeutic Target For Controlling Inflammation In Human Brains?

Walker

Lue

2013

Future Neurol.

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CD200 and its receptor, CD200 receptor (CD200R), have uniaue roles in controlling damaging inflammatory processes. At present, the only identified function for CD200 is as a ligand for CD200R. These proteins interact resulting in the activation of anti-inflammatory signaling by CD200R-expressing cells. When this interaction becomes deficient with aging or disease, chronic inflammation occurs, Experimental animal studies have demonstrated the consequences of disrupting CD200–CD200R interactions in the brain, but there have been few studies in human brains. Deficiency in neuronal CD200 may explain the chronic inflammation in human neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis; however, deficits in the microglial expression of CD200R may also be of functional significance. The purpose of this review is to assess the data regarding the role of CD200–CD200R interactions in relation to the brain in order to determine if this could be a therapeutic target for human brain diseases with inflammatory components, and what additional studies are needed.

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Section: Biology Of Cd200 and The Cd200rmentioning

confidence: 99%

Understanding the Neurobiology of Cd200 and the Cd200 Receptor: A Therapeutic Target For Controlling Inflammation In Human Brains?

Walker

Lue

2013

Future Neurol.

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“…However, in addition to the inhibitory CD200R1, there is a series of activation receptors (CD200AR2, 3, 4, and 5) in mice (16). By using specific synthetic peptide ligands (CD200AR-L) that we identified through protein sequencing and structural analyses of CD200 (10), we developed a peptide-based strategy to engage these activation receptors on immune cells (10) and demonstrated that the inhibitory effects of CD200 protein can be surmounted by selectively engaging CD200ARs (11,17).…”

Section: Introductionmentioning

confidence: 99%

CD200 Checkpoint Reversal: A Novel Approach to Immunotherapy

Xiong

Mesias

Pluhar

et al. 2020

Clinical Cancer Research

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◥ Purpose: Advances in immunotherapy have revolutionized care for some patients with cancer. However, current checkpoint inhibitors are associated with significant toxicity and yield poor responses for patients with central nervous system tumors, calling into question whether cancer immunotherapy can be applied to glioblastoma multiforme. We determined that targeting the CD200 activation receptors (CD200AR) of the CD200 checkpoint with a peptide inhibitor (CD200AR-L) overcomes tumor-induced immunosuppression. We have shown the clinical efficacy of the CD200AR-L in a trial in companion dogs with spontaneous high-grade glioma. Addition of the peptide to autologous tumor lysate vaccines significantly increased the median overall survival to 12.7 months relative to tumor lysate vaccines alone, 6.36 months.Experimental Design: This study was developed to elucidate the mechanism of the CD200ARs and develop a humanized peptide inhibitor. We developed macrophage cell lines with each of four CD200ARs knocked out to determine their binding specificity and functional response. Using proteomics, we developed humanized CD200AR-L to explore their effects on cytokine/chemokine response, dendritic cell maturation and CMV pp65 antigen response in human CD14 þ cells. GMP-grade peptide was further validated for activity.Results: We demonstrated that the CD200AR-L specifically targets a CD200AR complex. Moreover, we developed and validated a humanized CD200AR-L for inducing chemokine response, stimulating immature dendritic cell differentiation and significantly enhanced an antigen-specific response, and determined that the use of the CD200AR-L downregulated the expression of CD200 inhibitory and PD-1 receptors.Conclusions: These results support consideration of a CD200AR-L as a novel platform for immunotherapy against multiple cancers including glioblastoma multiforme.

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“…The ligand CD200, also a member of the IgSF, is widely expressed and therefore CD200R-CD200 interactions are involved in many immune-regulatory processes [156,158]. For instance, CD200R was found to attenuate inflammation in neurodegenerative and cardiovascular disorders, and also in allergy [159]. Pathogens and cancer cells may have evolved means that result in immune evasion: CD200 is up-regulated in leukemias and large DNA viruses including herpes-and poxviruses, seem to bind CD200 [159][160][161].…”

Section: Cd200rmentioning

confidence: 99%

Immunoreceptors on neutrophils

Rees

Szilagyi

Kuijpers

et al. 2016

Seminars in Immunology

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Neutrophils play a critical role in the host defense against infection, and they are able to perform a variety of effector mechanisms for this purpose. However, there are also a number of pathological conditions, including autoimmunity and cancer, in which the activities of neutrophils can be harmful to the host. Thus the activities of neutrophils need to be tightly controlled. As in the case of other immune cells, many of the neutrophil effector functions are regulated by a series of immunoreceptors on the plasma membrane. Here, we review what is currently known about the functions of the various individual immunoreceptors and their signaling in neutrophils. While these immunoreceptors allow for the recognition of a diverse range of extracellular ligands, such as cell surface structures (like proteins, glycans and lipids) and extracellular matrix components, they commonly signal via conserved ITAM or ITIM motifs and their associated downstream pathways that depend on the phosphorylation of tyrosine residues in proteins and/or inositol lipids. This allows for a balanced homeostatic regulation of neutrophil effector functions. Given the number of available immunoreceptors and their fundamental importance for neutrophil behavior, it is perhaps not surprising that pathogens have evolved means to evade immune responses through some of these pathways. Inversely, some of these receptors evolved to specifically recognize these pathogens. Finally, some interactions mediated by immunoreceptors in neutrophils have been identified as promising targets for therapeutic intervention.

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CD200/CD200R Paired Potent Inhibitory Molecules Regulating Immune and Inflammatory Responses; Part II : CD 200/CD200R Potential Clinical Applications

Cited by 17 publications

References 49 publications

Understanding the Neurobiology of Cd200 and the Cd200 Receptor: A Therapeutic Target For Controlling Inflammation In Human Brains?

Understanding the Neurobiology of Cd200 and the Cd200 Receptor: A Therapeutic Target For Controlling Inflammation In Human Brains?

CD200 Checkpoint Reversal: A Novel Approach to Immunotherapy

Immunoreceptors on neutrophils

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