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Casitas B-lineage-lymphoma-b is a key regulator of peripheral tolerance in systemic lupus erythematosus.
MedLine Citation:
PMID:  23280105     Owner:  NLM     Status:  Publisher    
OBJECTIVE: Analyze the expression and modulation of TCR signaling dependent on Cbl-b in T cells from SLE patients upon tolerogenic stimuli. METHODS: Twenty SLE patients (active and remission) and 20 healthy controls were included. Cbl-b expression was measured by RT-PCR and western blot in peripheral CD4(+) T cells from patients and controls upon anergy induction. Cell proliferation was measured by CFSE. Cytokine production was analyzed by luminometry and activation markers surface expression by flow cytometry. Transfection assays were made to overexpress Cbl-b and TCR kinases phosphorylation was evaluated. RESULTS: We found that CD4(+) T cells from SLE patients displayed resistance to anergy (increased proliferation, IL-2 production, and expression of activation and costimulatory markers) that was also associated with altered Cbl-b expression. Upon ionomycin treatment, primary T cells showed enhanced mitogen-activated protein kinase (MAPK) activity and decreased Akt phosphorylation, which was representative of the anergic state. In T cells from lupus patients, Cbl-b overexpression led to increased p-MAPK expression, which indicates the reversibility of anergy resistance. CONCLUSIONS: Our data suggest that abnormal peripheral tolerance in SLE is caused by Cbl-b deficiency and that this ubiquitin ligase plays a key role in regulating TCR signalling during the induction of peripheral tolerance. © 2012 American College of Rheumatology.
Diana Gómez-Martín; María Ibarra-Sánchez; Jorge Romo-Tena; José Cruz-Ruíz; José Esparza-López; Miguel Galindo-Campos; Mariana Díaz-Zamudio; Jorge Alcocer-Varela
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-21
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-1-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
Department of Immunology and Rheumatology. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
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