Molecular Mechanisms of CD200 Inhibition of Mast Cell Activation

Zhang, Shuli; Cherwinski, Holly; Sedgwick, Jonathon D.; Phillips, Joseph H.

doi:10.4049/jimmunol.173.11.6786

Cited by 215 publications

(227 citation statements)

References 48 publications

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“…CD200 is widely expressed and has a short intracellular tail which does not contain signalling motifs, whereas CD200R has a longer intracellular tail that contains three tyrosines, one of which is located in an NPXY motif . However, CD200R does not contain the common immunoreceptor tyrosine-based inhibition motifs (ITIMs) and has been described to regulate cellular activation via recruitment of the adaptor molecules Dok-1 and Dok-2 to the tyrosines in its intracellular tail (Zhang et al, 2004;Zhang and Phillips, 2005).…”

Section: E-mail Address: Lmeyaard@umcutrechtnl (L Meyaard)mentioning

confidence: 99%

The inhibitory CD200R is differentially expressed on human and mouse T and B lymphocytes

Rijkers

Ruiter

Baridi

et al. 2008

Molecular Immunology

118

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To ensure an adequate response against pathogens and prevent unwanted self-reactivity, immune cells need to functionally express both activating and inhibitory receptors. CD200R is an inhibitory receptor mainly expressed on myeloid cells that down-modulates cellular activation both in vivo and in vitro. Although previously mainly studied as a regulator of myeloid function, we now show that CD200R is differentially expressed on human and mouse T-cell subsets. In both species, CD4 + T cells express higher amounts of CD200R than CD8 + T cells, and memory cells express higher amounts of CD200R than naïve or effector cells. CD200R expression is up-regulated on both CD4 + and CD8 + T cells after stimulation in vitro. Furthermore, we show CD200R expression on human and mouse B cells. In human tonsils, CD200R is differentially expressed on B cells, with high expression on memory cells and plasmablasts. Mice lacking the ligand for CD200R, CD200 −/− mice, do not show abnormal composition of the lymphocyte compartment and have normal B cell responses to antigenic challenge. Although the functional implications remain to be elucidated, the expression of CD200R on lymphocytes suggests a much broader role for CD200R-mediated immune regulation than previously anticipated.

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Section: E-mail Address: Lmeyaard@umcutrechtnl (L Meyaard)mentioning

confidence: 99%

The inhibitory CD200R is differentially expressed on human and mouse T and B lymphocytes

Rijkers

Ruiter

Baridi

et al. 2008

Molecular Immunology

118

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“…14,15 If we attempt to reconstitute and de-activate macrophage function (by direct ligation of CD200R with anti-CD200R monoclonal antibodies or by a CD200Fc), attenuation of retinal or CNS inflammation can be achieved 14,16 as well as regulation of other myeloid cells, including mast cells in the lung. [17][18][19][20] How do we keep the peace? A premise lies that there is continual immunosurveillance, akin to CNS, and that alongside the immune cell inhabitants of the retina and choroid, together achieve constant sensing to respond to danger signals.…”

Section: Keeping the Peacementioning

confidence: 99%

Doyne lecture 2016: intraocular health and the many faces of inflammation

Dick

2016

Eye

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Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses.

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“…These interactions produce altered graft rejection and suppress inflammation in a mouse model of collagen-induced arthritis (7). In contrast, CD200 interacting with alternate CD200R isoforms expressed at the cell surface of myeloid-derived cells fails to produce direct immunosuppression in similar assays (8), and distinct biochemical signaling pathways have been reported to be activated following interaction of CD200 with different CD200R family members (9,10). Triggering of alternate CD200R isoforms seems to be instrumental in directing differentiation of bone marrow precursors in vitro into dendritic cell (DC) 3 populations that are able in turn to induce development of CD4 ϩ CD25 ϩ Foxp3 ϩ regulatory T cells (Treg) with immunoregulatory properties in a mouse transplant model (skin graft rejection) (11).…”

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confidence: 99%

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

Gorczynski

Khatri

Lee

et al. 2008

The Journal of Immunology

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In previous studies we reported that while interaction between the relatively ubiquitously expressed molecule CD200 and one of its receptors, CD200R1, resulted in direct suppression of alloreactivity, engagement of alternate receptors led instead to altered differentiation of dendritic cells (DCs) from marrow precursors, which could in turn foster development of Foxp3+ regulatory T cells. We have explored this effect of engagement of alternate receptors by using a monoclonal agonist Ab to CD200R2 and investigating expression of TLRs on DCs induced in vivo and in vitro after CD200 stimulation in mice in which the gene encoding CD200R1 was deleted. CD200 stimulation was achieved by using either a soluble form of CD200 (CD200Fc) or overexpression of CD200 as a doxycycline-inducible transgene. Although broadly similar effects were seen, consistent with the hypothesis that triggering of CD200R2 does produce DCs with a characteristic TLR repertoire, there are subtle differences in suppression of alloreactivity achieved by CD200 delivered in these two manners, which is consistent with a complexity of CD200:CD200R engagement not previously appreciated.

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Molecular Mechanisms of CD200 Inhibition of Mast Cell Activation

Cited by 215 publications

References 48 publications

The inhibitory CD200R is differentially expressed on human and mouse T and B lymphocytes

The inhibitory CD200R is differentially expressed on human and mouse T and B lymphocytes

Doyne lecture 2016: intraocular health and the many faces of inflammation

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

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