The CD300 molecules regulate monocyte and dendritic cell functions

Clark, Georgina J.; Ju, Xinsheng; Azlan, Maryam; Tate, Courtney; Ding, Yitian; Hart, Derek N.J.

doi:10.1016/j.imbio.2009.06.004

Cited by 32 publications

(35 citation statements)

References 40 publications

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“…Naive B cells express low levels of CD300a, whereas memory B cells and plasma cells express variable levels, and germinal center B cells are negative for CD300a cell surface expression (16). In the myeloid lineage, CD300a is detected on the surface of plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), monocytes, macrophages, neutrophils, eosinophils, basophils, and mast cells (13,(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Regulation Of Expressionmentioning

confidence: 99%

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

Zenarruzabeitia

Vitallé

Eguizábal³

et al. 2015

The Journal of Immunology

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The CD300a inhibitory receptor belongs to the CD300 family of cell surface molecules that regulate a diverse array of immune cell processes. The inhibitory signal of CD300a depends on the phosphorylation of tyrosine residues embedded in ITIMs of the cytoplasmic tail. CD300a is broadly expressed on myeloid and lymphoid cells, and its expression is differentially regulated depending on the cell type. The finding that CD300a recognizes phosphatidylserine and phosphatidylethanolamine, two aminophospholipids exposed on the outer leaflet of dead and activated cells, has shed new light on its role in the modulation of immune functions and in its participation in the host response to several diseases states, such as infectious diseases, cancer, allergy, and chronic inflammatory diseases. This review summarizes the literature on CD300a expression, regulation, signaling pathways, and ligand interaction, as well as its role in fine tuning immune cell functions and its clinical relevance.

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Section: Regulation Of Expressionmentioning

confidence: 99%

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

Zenarruzabeitia

Vitallé

Eguizábal³

et al. 2015

The Journal of Immunology

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“…12,23 We looked at the expression of CD300a on human B cells from peripheral blood and tonsils using the specific anti-CD300a mAb, clone E59.126, which recognizes a unique epitope in CD300a. 13,24 We performed multicolor flow cytometric analyses and showed that there is a significant proportion of peripheral blood and tonsil B cells, identified by the expression of CD19, which express CD300a ( Figure 1A). …”

Section: Cd300a Is Differentially Expressed On Human B-cell Subsetsmentioning

confidence: 99%

CD300a is expressed on human B cells, modulates BCR-mediated signaling, and its expression is down-regulated in HIV infection

Silva

Moir

Kardava

et al. 2011

Blood

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IntroductionAn adequate immune response is the result of a fine balance between a multitude of activating and inhibitory signals, and disruption of this delicate balance can lead to autoimmunity or immunodeficiency. Activation signals can be negatively regulated by cell surface receptors bearing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tail. 1 Examples of ITIM-containing receptors expressed on B cells include Fc␥RIIB, CD22, CD72, paired Ig-like receptor (PIR)-B, CD85j, Fc receptorlike (FCRL)4, and CD305. [2][3][4][5] The coligation of the B-cell receptor (BCR) and ITIM-containing receptors results in the attenuation of BCR-mediated signals. 3,5,6 Depending on the developmental stage or activation status, B cells express different sets of inhibitory receptors on their cell surface. 5,7,8 For example, CD305 is highly expressed on naive human B cells, and its expression is low in memory B cells, 5 whereas FCRL4 is mostly expressed on a subset of memory cells and is almost absent on naive B cells. 7 The expression of certain ITIM-containing receptors, such as FCRL4 and CD85j, is increased in specific B-cell subsets that are substantially expanded in certain disease settings, such as in HIV-infected viremic patients with high viral loads 9 and in persons exposed to Plasmodium falciparum. 10 It is acknowledged that the deregulation of the expression of these receptors contributes to the B-cell dysfunctions observed in HIV and malarial chronic infections. 11 CD300a belongs to the CD300 family of activating/inhibitory receptors whose genes are clustered in human chromosome 17. 12 CD300a is a type I transmembrane receptor with an IgV-like extracellular domain and a cytoplasmic tail that has 3 classic ITIM motifs 12,13 and is expressed on cells of both lymphoid and myeloid lineages. 12 Its ligation is capable of inhibiting natural killer cell-mediated cytotoxicity, 13,14 Fc␥RIIa-mediated reactive oxygen species production and Ca 2ϩ flux in neutrophils, 15 Fc⑀RI-mediated activation of mast cells, 16 and eosinophil responses to eotaxin, granulocyte-macrophage colony-stimulating factor, and IL-5. 17 In a murine model of asthma, treatment of mice with a bispecific antibody linking CD300a to CCR3 reversed remodeling and airway inflammation. 18 In another in vivo study, a bispecific antibody fragment linking CD300a to IgE was able to abrogate allergic reactions. 19 Finally, a recent study showed that a bispecific antibody that links kit with CD300a abrogates the allergic reaction induced by stem cell factor in a model of anaphylaxis. 20 All these studies highlight the potential of specifically targeting CD300a for therapeutic purposes.In this study, we demonstrate that CD300a is differentially expressed on human B-cell subsets and can function as a negative regulator of BCR-mediated signaling. Furthermore, we show that the expression of this receptor is deregulated in HIV-infected patients, suggesting a potential role for CD300a in HIV-associated disease progression. The online version of thi...

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“…In contrast, activating receptors usually present short cytoplasmic tails lacking any signaling motifs. Alternatively, they present a positively charged amino acid residue within their transmembrane domain that enables the interaction with immunoreceptor tyrosine-based activating motif (ITAM) 5 -bearing adaptor proteins (Fc⑀R␥, CD3, and DAP12 (DNAX-activating protein of 12 kDa)), which contain a complementary negative charge in the same domain. Ligand-induced phosphorylation of ITAMs leads to the recruitment of tandem Src homology 2 domaincontaining tyrosine kinases, such as Syk and ZAP-70, to transduce activating signals (1).…”

mentioning

confidence: 99%

“…The human CD300 family of immunoreceptors belongs to the superfamily of immunoglobulin receptors, and the genes that encode for the different members are clustered on human chromosome 17q25.1 (4,5). All of them are found exclusively in myeloid cells, with the exception of CD300a that is additionally expressed in certain subsets of T and NK cells.…”

mentioning

confidence: 99%

Cloning and Characterization of CD300d, a Novel Member of the Human CD300 Family of Immune Receptors

Comas-Casellas

Martínez-Barriocanal

Miró

et al. 2012

Journal of Biological Chemistry

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Background: Leukocyte function is regulated by the balance between activating and inhibitory signals deliver by immune receptors. Results: We present the cloning and molecular characterization of a novel CD300 member, CD300d. Conclusion:The function of CD300d is related to the regulation of the expression and function of other CD300 receptors. Significance: A new mechanism of regulation of myeloid cell activation is described.

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The CD300 molecules regulate monocyte and dendritic cell functions

Cited by 32 publications

References 40 publications

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

CD300a is expressed on human B cells, modulates BCR-mediated signaling, and its expression is down-regulated in HIV infection

Cloning and Characterization of CD300d, a Novel Member of the Human CD300 Family of Immune Receptors

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