CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor

Rygiel, Tomasz P.; Karnam, Guruswamy; Goverse, Gera; Marel, Arnold P. J. van der; Greuter, Mascha; Schaarenburg, Rosanne A. van; Visser, W. J.; Brenkman, Arjan B.; Molenaar, Rosalie; Hoek, Robert M.; Mebius, Reina E.; Meyaard, Linde

doi:10.1038/onc.2011.477

Cited by 67 publications

(56 citation statements)

References 45 publications

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“…However, challenging these mice, for instance by viral and bacterial infections, induced tumor formation and induced autoimmunity, leads to overt phenotypes. [20], [21], [24] CD200-CD200R axis also affects Toll-like receptor 2 and 4 responses, and thereby facilitates protection against excessive inflammatory responses [25], [26]. In the past, we have shown that Toll-like receptor 2 and 4 play a crucial role in arteriogenesis [27].…”

Section: Discussionmentioning

confidence: 99%

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The CD200-CD200 Receptor Inhibitory Axis Controls Arteriogenesis and Local T Lymphocyte Influx

et al. 2014

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The role of the CD200 ligand-CD200 receptor (CD200-CD200R) inhibitory axis is highly important in controlling myeloid cell function. Since the activation of myeloid cells is crucial in arteriogenesis, we hypothesized that disruption of the CD200-CD200R axis promotes arteriogenesis in a murine hindlimb ischemia model. Female Cd200−/− and wildtype (C57Bl/6J) mice underwent unilateral femoral artery ligation. Perfusion recovery was monitored over 7 days using Laser-Doppler analysis and was increased in Cd200−/− mice at day 3 and 7 after femoral artery ligation, compared to wildtype. Histology was performed on hindlimb muscles at baseline, day 3 and 7 to assess vessel geometry and number and inflammatory cell influx. Vessel geometry in non-ischemic muscles was larger, and vessel numbers in ischemic muscles were increased in Cd200−/− mice compared to wildtype. Furthermore, T lymphocyte influx was increased in Cd200−/− compared to wildtype. CD200R agonist treatment was performed in male C57Bl/6J mice to validate the role of the CD200-CD200R axis in arteriogenesis. CD200R agonist treatment after unilateral femoral artery ligation resulted in a significant decrease in vessel geometry, perfusion recovery and T lymphocyte influx at day 7 compared to isotype treatment. In this study, we show a causal role for the CD200-CD200R inhibitory axis in arteriogenesis in a murine hindlimb ischemia model. Lack of CD200R signaling is accompanied by increased T lymphocyte recruitment to the collateral vasculature and results in enlargement of preexisting collateral arteries.

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Section: Discussionmentioning

confidence: 99%

“…We previously showed that mice lacking CD200 suffer from increased immunopathology in response to influenza virus infections, compared to wildtype controls [20], for which T lymphocytes are essential. On the other hand, the absence of CD200-CD200R signaling breaks tumor tolerance and inhibits outgrowth of endogenous tumors [21].…”

Section: Introductionmentioning

confidence: 99%

The CD200-CD200 Receptor Inhibitory Axis Controls Arteriogenesis and Local T Lymphocyte Influx

et al. 2014

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“…Also CD200R expression was shown on mouse and human mast cells, in these cells, CD200R engagement inhibited mast cell degranulation and decreased IL-13 and TNF secretions (Cherwinski et al, 2005). From the other point of view, CD200-CD200R signalling could benefit tumor cells and CD200 gene knockout mice were resistance to tumor induction; lymph nodes of these mice contained more regulatory T cells which tend to home tumours (Rygiel et al, 2012). Moreover, CD200 over-expression in transgenic mice could facilitate tumor cell metastasis while neutralising CD200 could result in decreased metastasis and increased antitumor cytotoxic lymphocytes (Gorczynski et al, 2011).…”

Section: Introductionmentioning

confidence: 95%

Structural properties of a viral orthologue of cellular CD200 protein: KSHV vOX2

et al. 2015

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Kaposi׳s sarcoma-associated herpesvirus (KSHV) vOX2 is a cell surface glycoprotein expressed during viral lytic replication to suppress host inflammatory reactions. Here we have characterised vOX2 with biochemical, biophysical and bioinformatics tools and as a result propose a 3-dimensional model for vOX2 based on structural and functional homology with the PD-L1 protein. To validate this model, vOX2 was characterised by analytical ultracentrifugation (AUC) and circular dichroism spectroscopy (CD). The results identified the potential glycosylation sites and revealed that vOX2 is predominantly a beta-folded molecule with an RGD adhesion motif exposed on the C-terminal domain. The protein exists in monomer-dimer equilibrium similar to its IgV-type folded homologues, with 30-36% glycosylation and the molecular weight of the extracellular fragment of molecule is 32.0-33.6 kDa, much less than 50 kDa. Thus, the structural similarity to PD-L1 verifies its immunomodulatory potential and the RGD motif suggests an adhesive capacity.

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“…It has been demonstrated that lack of CD200R signaling inhibits outgrowth of endogenous tumours [34] (Rygiel et al, 2012). An interesting way to enhance the CD200-CD200R blockade is to combine the blocking agent with TLR7 stimulation.…”

Section: Dendritic Cells In Therapymentioning

confidence: 99%

Immune Cells As Targets and Tools For Cancer Therapy

Tonecka¹,

Pilch²,

Ramji³

et al. 2017

Immunotherapy

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CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor

Cited by 67 publications

References 45 publications

The CD200-CD200 Receptor Inhibitory Axis Controls Arteriogenesis and Local T Lymphocyte Influx

The CD200-CD200 Receptor Inhibitory Axis Controls Arteriogenesis and Local T Lymphocyte Influx

Structural properties of a viral orthologue of cellular CD200 protein: KSHV vOX2

Immune Cells As Targets and Tools For Cancer Therapy

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