SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda

Jw, Tjiu; Pj, Lin; Wu, Wei-Hsin; Yp, Cheng; Hc, Chiu; Hy, Thong; Chiang, Bor‐Luen; Yang, Wei‐Shiung; Jee, Shiou‐Hwa

doi:10.1111/j.1365-2133.2010.10059.x

Cited by 46 publications

(36 citation statements)

References 34 publications

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“…In the later stages of the disease, there are rare reports of malignant melanoma arising within the areas of hyperkeratosis in Mal de Meleda [26][27][28].…”

Section: Clinical Patternsmentioning

confidence: 99%

Mal de Meleda: A Focused Review

Pérez

Khachemoune

2015

Am J Clin Dermatol

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Mal de Meleda is a rare autosomal recessive palmoplantar keratoderma (PPK) disease with an estimated prevalence of 1:100,000. Clinically, the onset of the disease is typically soon after birth and features a transgrediens (plantar surface progressing to dorsal surface) and progrediens (worsening with age) pattern of hyperkeratosis of the palms and soles. The disease can feature other potentially disfiguring effects on the hands and feet that can severely impact function. Histologically, the lesions show hyperkeratosis and acanthosis without epidermolysis in the epidermis, accompanied by perivascular lymphocytic infiltrate in the dermis. Secreted LY6/urokinase-type plasminogen activator receptor (uPAR)-related protein-1 (SLURP-1) genetic mutations are implicated in Mal de Meleda. SLURP-1 is involved in mediation of inflammation as well as keratinocyte apoptosis regulation. Because the disease is so rare, there are no set guidelines for management, but the accepted approach tends to include oral acitretin plus topical keratolytic therapy. Genetic counseling should also be offered. This focused review highlights the clinical and histological features, differential diagnoses, genetic background, and the current thoughts on management of Mal de Meleda.

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“…In the later stages of the disease, there are rare reports of malignant melanoma arising within the areas of hyperkeratosis in Mal de Meleda [26][27][28].…”

Section: Clinical Patternsmentioning

confidence: 99%

Mal de Meleda: A Focused Review

Pérez

Khachemoune

2015

Am J Clin Dermatol

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“…SLURP1 and SLUPR2 have been identified in Mal de Meleda and hyperproliferative skin of patients with psoriasis vulgaris, respectively (67,68). SLURP1 regulates epidermal homeostasis, inflammation, keratinization, and programmed cell death as well as tumorigenesis of the colon, survival of fibroblasts, and T cell activation (69-72). SLURP2 plays a role not only in kerationcyte hyperproliferation and T cell differentiation/activation but is also competes with SLURP1 for the human nicotinic acetylcholine receptor (hAChR), thereby delaying keratinocyte differentiation and preventing apoptosis (68,73).…”

Section: Functional Analysis Of Ly-6/upar Moleculesmentioning

confidence: 99%

Characterization and function of human Ly-6/uPAR molecules

Kong¹,

Park²

2012

BMB Reports

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Human Ly-6/uPAR molecules are a superfamily composed of two subfamilies; one is the membrane bound proteins with a GPI-anchor and the other are secreted proteins without the GPI-anchor. Ly-6/uPAR molecules have remarkable amino acid homology through a distinctive 8-10 cysteine-rich domain that is associated predominantly with O-linked glycans. These molecules are encoded by multiple tightly linked genes located on Chr. 8q23, and have a conserved genomic organization. Ly-6/uPAR molecules have an interesting expression pattern during hematopoiesis and on specific tumors indicating that Ly-6/uPAR molecules are associated with development of the immune system and carcinogenesis. Thus, Ly-6/uPAR molecules are useful antigens for diagnostic and therapeutic targets. This review summarizes our understanding of human Ly-6/uPAR molecules with regard to molecular structure as well as what is known about their function in normal and malignant tissues and suggest Ly-6/uPAR molecules as target antigens for cancer immunotherapy. [BMB Reports 2012; 45(11): 595-603]

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“…A novel paradigm of cell regulation via nAChRs has been discovered in studies of the autosomal recessive disease palmoplantar keratoderma featuring mutation of secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein- (SLURP-) 1 and impaired T-cell activity [43]. SLURP-2 expression was also discovered in the skin [44].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes

Chernyavsky

Galitovskiy

Shchepotin

et al. 2014

BioMed Research International

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A search for novel and more efficient therapeutic modalities of inflammatory bowel disease (IBD) is one of the most important tasks of contemporary medicine. The anti-inflammatory action of nicotine in IBD might be therapeutic, but its toxicity due to off-target and nonreceptor effects limited its use and prompted a search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and -2—the physiological nicotinergic substances produced by the human intestinal epithelial cells (IEC) and immunocytes—can mimic the anti-inflammatory effects of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T-cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of IL-8 by CCL-241, and IFNγ-induced upregulation of ICAM-1 in both IEC types. rSLURP-2 inhibited IL-1β-induced secretion of IL-6 and TLR4- and TLR9-dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1 decreased production of TNFα by T-cells, downregulated IL-1β and IL-6 secretion by macrophages, and moderately upregulated IL-10 production by both types of immunocytes. SLURP-2 downregulated TNFα and IFNγR in T-cells and reduced IL-6 production by macrophages. Combining both SLURPs amplified their anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on enterocytes, colonocytes, T cells, and macrophages may help develop novel effective treatments of IBD.

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SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda

Abstract: Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.

Cited by 46 publications

References 34 publications

Mal de Meleda: A Focused Review

Mal de Meleda: A Focused Review

Characterization and function of human Ly-6/uPAR molecules

Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes

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