| Autor: |
Jeng-Wei Tjiu, Wei-Shiung Yang, Hsien-Ching Chiu, Bor-Luen Chiang, Thong Hy, Wu Wh, Lin Pj, Shiou-Hwa Jee, Cheng Yp |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
British Journal of Dermatology. 164:47-53 |
| ISSN: |
0007-0963 |
| DOI: |
10.1111/j.1365-2133.2010.10059.x |
| Popis: |
Summary Background Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. Objectives To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. Methods Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. Results PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 μg mL−1 recombinant human SLURP-1 protein. Conclusions 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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