CD300 molecule regulation of human dendritic cell functions

Gasiorowski, Robin; Ju, Xinsheng; Hart, Derek N.J.; Clark, Georgina J.

doi:10.1016/j.imlet.2012.10.005

Cited by 24 publications

(25 citation statements)

References 70 publications

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“…CD300a plays a pathogenic role in a number of diseases, including asthma, cutaneous anaphylaxis, pulmonary inflammation, acute lymphoblastic leukemia, ulcerative colitis, Alzheimer's disease and AIDS, 12,26,56 and the potential of CD300a as a therapeutic target for allergic and autoimmune diseases has been proposed. 10,12,23,24 CD300a has also been implicated by genome-wide association studies in the development of chronic inflammatory diseases, such as psoriasis, atopic dermatitis and rheumatoid arthritis.…”

Section: Discussionmentioning

confidence: 99%

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Identification of CD300a as a new hypoxia-inducible gene and a regulator of CCL20 and VEGF production by human monocytes and macrophages

et al. 2013

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Peripheral blood monocytes are recruited to inflammatory and tumor lesions where they undergo terminal differentiation into macrophages. Monocytes/macrophages integrate stimulatory and inhibitory signals present in the pathologic microenvironment through a defined repertoire of cell surface receptors, and deregulated expression of these molecules may result in amplification of inflammation or establishment of immune escape mechanisms. Characterization of the expression and function of these receptors is required for a better understanding of the regulation of monocyte/macrophage activity at pathologic sites. Hypoxia is a common feature of many pathological situations and an important regulator of monocyte/macrophage pro-inflammatory responses. In this study, we identify the leukocyte membrane antigen, CD300a, a member of the CD300 superfamily of immunoregulatory receptors, as a new hypoxia-inducible gene in primary human monocytes and monocyte-derived macrophages. CD300a mRNA up-regulation by hypoxia was rapid and reversible, paralleled by increased surface protein expression, and mediated by hypoxia-inducible factor-1α. CD300a induction was also triggered by the hypoxia-mimetic agent, desferrioxamine. CD300a exhibited both activating and inhibitory potential, differentially regulating CCL20 and vascular endothelial growth factor pro-inflammatory cytokine production by monocytes/macrophages upon triggering by an agonist Ab. These results suggest that CD300a induction by the hypoxic environment represents a mechanism of regulation of monocyte/macrophage pro-inflammatory responses at pathologic sites.

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Section: Discussionmentioning

confidence: 99%

“…24 However, CD300a is also endowed with an activating potential, as shown by its ability to induce IFNa/b secretion by CpG-stimulated human plasmacytoid dendritic cells (DCs). 15 CD300a is expressed on MP, 13,25,26 but its regulation and function in these cells remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Identification of CD300a as a new hypoxia-inducible gene and a regulator of CCL20 and VEGF production by human monocytes and macrophages

et al. 2013

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“…The CD300 family of molecules regulates a large range of immune cell processes via their paired activating and inhibitory receptors [9,20]. Among these molecules, it has been shown that the activating members, CD300b and CD300e, and the inhibitory receptors, CD300a and CD300f, have a prominent role in regulating functions of human primary monocytes and monocytic cell lines [15,16,19,34,35].…”

Section: Discussionmentioning

confidence: 99%

“…The human activating members of this family include CD300b, CD300c, CD300d and CD300e, and associate with adaptor molecules such as FcRγ chain (FcεRIγ), DAP (DNAX-activating protein) 12 or DAP10 [9,16,17,18,19]. The inhibitory receptors include CD300a and CD300f [9,20]. Phylogenetic analyses have shown that CD300a and CD300c are paired receptors with a homology in their extracellular immunoglobulin domain higher than 80% [21,22].…”

Section: Introductionmentioning

confidence: 99%

CD300c is an Activating Receptor Expressed on Human Monocytes

Simhadri

Mariano²,

Gil-Krzewska

et al. 2013

J Innate Immun

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Human CD300 molecules comprise a family of receptors that regulate many immune cell processes. They are mostly expressed on myeloid cells, although expression of two members, CD300a and CD300c, has also been described on lymphocytes. However, due to the lack of specific antibodies that distinguish between these two receptors, it has been difficult to determine the expression pattern and function of CD300a and CD300c in primary cells. Here, we have identified a specific monoclonal antibody, clone TX45, that recognizes only CD300c and show that within freshly isolated blood leukocytes, monocytes are the only cells that express CD300c on the cell surface. In vitro differentiation experiments revealed that CD300c is differentially expressed on different monocyte-derived cells, including macrophages and dendritic cells. Furthermore, TLR ligands LPS and flagellin dynamically regulate the expression of CD300c. Cross-linking of this receptor with clone TX45 monoclonal antibody induced calcium mobilization, upregulation of the costimulatory molecule CD86 and the production of inflammatory cytokines. Importantly, LPS-mediated production of inflammatory cytokines by monocytes was further enhanced if CD300c was simultaneously engaged by the agonist antibody. Altogether, our results show that human CD300c is an activating receptor expressed on monocytes and that it has a potential role in inflammatory responses.

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“…CTX feeding triggers NF-B activation and cytokine expression in the mesenteric lymph node and Peyer's patch cells Gasiorowski et al, 2013). For example, DAP12-coupled receptors include TREM2 and LMIR5/CD300b.…”

Section: Introductionmentioning

confidence: 99%