Novel immunoglobulin superfamily gene cluster, mapping to a region of human chromosome 17q25, linked to psoriasis susceptibility

Speckman, Rebecca A.; Daw, Jil; Helms, Cynthia; Duan, Shenghui; Cao, Li; Taillon-Miller, Patricia; Kwok, Pui‐Yan; Menter, Alan; Bowcock, Anne M.

doi:10.1007/s00439-002-0851-y

Cited by 74 publications

(72 citation statements)

References 39 publications

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“…This family is encoded in a region of human chromosome 17 (17q24-q25), and as in other inhibitory receptor families, the CMRF-35 cluster includes ITIM-bearing molecules as well as short-tailed proteins [16,17]. Members of this gene family have been shown to be expressed on cells of different hematopoietic lineages, such as T cell subsets, B lymphocytes, NK cells, monocytes, macrophages, and granulocytes [18].…”

Section: Discussionmentioning

confidence: 99%

“…It is conceivable that together with other inhibitory molecules, this receptor may contribute to keep a threshold of activation, counterbalancing the function of other triggering receptors of the same [16] or other families expressed on myeloid cells (i.e. FcR, TREM, ILT).…”

Section: Discussionmentioning

confidence: 99%

“…FcR, TREM, ILT). In this regard, studies linking this gene family to psoriasis susceptibility [16] suggest that these receptors may have an important immunoregulatory role controlling inflammation. The identification of the IREM-1 physiological ligand becomes an essential step to establish the biological relevance of this molecule in the regulation of myeloid cell functions.…”

Section: Discussionmentioning

confidence: 99%

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IREM‐1 is a novel inhibitory receptor expressed by myeloid cells

et al. 2004

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Using a three-hybrid strategy, we have identified a novel cell surface molecule which interacts with the Src homology 2 (SH2) domains of SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1), termed "immune receptor expressed on myeloid cells 1" (IREM-1). The full-length cDNA coding for a polypeptide of 290 amino acids presents an extracellular single V-type Ig domain, a transmembrane region and a cytoplasmic tail with five tyrosine residues, two of which are in the context of an immunoreceptor tyrosine-based inhibitory motif. Moreover, cDNA encoding for three other splicing forms of IREM-1, named IREM-1 splice variant (Sv)1, Sv2 and Sv3 were cloned by reverse transcription (RT)-PCR. The gene encoding for IREM-1 contains nine exons, is located on human chromosome 17 (17q25.1) and is homologous to previously identified molecules termed CMRF-35 and IRp60. RT-PCR, northern blot and FACS analysis with specific monoclonal antibodies indicated that IREM-1 is expressed on monocytes, granulocytes, and myeloid leukemia cell lines. Western blot analysis confirmed the recruitment of SHP-1 to IREM-1 and demonstrated that phosphotyrosine residue 205 is the main docking site for this interaction. Finally, crosslinking of IREM-1 results in the inhibition of FcRe-induced activation. Our results indicate that IREM-1 is a novel inhibitory receptor of the Ig superfamily in myeloid cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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IREM‐1 is a novel inhibitory receptor expressed by myeloid cells

et al. 2004

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“…CD300a is a receptor with three ITIM motifs within its cytoplasmic tail that belongs to a multigene family of activating/inhibitory receptors that are clustered in human chromosome 17 (17q25.1) (Speckman et al, 2003). CD300a is expressed on a variety of immune cells (Cantoni et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that the CD300a gene receptor ranks near the top of the human genes that show evidence of positive selection Nielsen et al, 2005), suggesting an important role for this receptor. Genetic studies have found that a nonsynonymous polymorphism within the immunoglobulin domain (R111Q) of the CD300a receptor is linked to psoriasis susceptibility (Speckman et al, 2003). Cross-linking of the CD300a receptor with a specific monoclonal antibody (mAb) has been shown to exert an inhibitory effect on natural killer (NK) cell activity through recruitment of src homology 2 domain (SH2)-containing tyrosine phosphatase (SHP)-1 and SHP-2 phosphatases (Cantoni et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The CD300a (IRp60) inhibitory receptor is rapidly up-regulated on human neutrophils in response to inflammatory stimuli and modulates CD32a (FcγRIIa) mediated signaling

Alvarez

Tang

Coligan

et al. 2008

Molecular Immunology

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To achieve an adequate response, cells of the immune system must be tightly regulated to avoid hypo-or hyper-responsiveness. One of the mechanisms used by the immune system to avoid excessive inflammation is the modulation of the response through inhibitory receptors containing immunoreceptor tyrosine based inhibitory motifs (ITIM). Here, we show that human neutrophils from peripheral blood express the ITIM containing CD300a (also known as IRp60 and CMRF-35H) receptor. By using the HL-60 differentiation model, we show that the expression of CD300a receptor is developmentally regulated. Stimulation of human neutrophils with LPS and GM-CSF increased the cell surface expression of CD300a as a result of the rapid translocation of an intracellular pool of the receptor to the cell surface. Co-ligation of CD300a with the immunoreceptor tyrosine based activating motif (ITAM) containing CD32a (FcγRIIa) activation receptor inhibited CD32a mediated signaling, whereas it did not inhibit Toll like receptor (TLR)-4 mediated reactive oxygen species (ROS) production. Therefore, at least for human neutrophils, the inhibitory signals mediated by the CD300a receptor may be selective in their action.

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Molecular Genetics and Immunopathogenesis of Psoriasis

Lepre

Zampatti

Novelli

et al. 2012

Encyclopedia of Life Sciences

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Psoriasis (OMIM #177900) is a common chronic disease of the skin that affects approximately 2–3% of the population. Typical lesions of psoriasis are characterised by red and scaly skin patches, usually found on the scalp, elbows and knees and often associated with severe arthritis. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. The onset of the disease is generally between 10 and 40 years of age. Type 1 begins at or before the age of 40 years; type II begins after the age of 40 years. Psoriasis is a complex disease due to the interaction between environmental factors and susceptibility alleles. Life style, diet, smoking, stress and infections are the best validated environmental factors predisposing to the pathology. During the past several years, researchers have identified different loci related to the disease, namely from PSORS1 to PSORS13 . Key Concepts: Multifactorial diseases are common disease due to the interaction between environmental factors and different susceptibility loci. Psoriasis, a chronic disease of the skin, is a common disease affecting approximately 2–3% of the population. Psoriasis is a complex disease. Different loci are known to be responsible for its development, together with some environmental factors, such us life style, diet, smoking, stress and infections. Immune system is responsible for the development of psoriasis: HLACw*06:02 is the best replicated and validated susceptibility allele. Understanding the genetic and epigenetic basis of psoriasis will help to further outline the molecular mechanism of onset and progression.

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Novel immunoglobulin superfamily gene cluster, mapping to a region of human chromosome 17q25, linked to psoriasis susceptibility

Cited by 74 publications

References 39 publications

IREM‐1 is a novel inhibitory receptor expressed by myeloid cells

IREM‐1 is a novel inhibitory receptor expressed by myeloid cells

The CD300a (IRp60) inhibitory receptor is rapidly up-regulated on human neutrophils in response to inflammatory stimuli and modulates CD32a (FcγRIIa) mediated signaling

Molecular Genetics and Immunopathogenesis of Psoriasis

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