Toll-like receptors regulate B cell cytokine production in patients with diabetes.
Diabetologia
; 53(7): 1461-71, 2010 Jul.
Article
in En
| MEDLINE
| ID: mdl-20383694
ABSTRACT
AIMS/HYPOTHESIS:
Understanding cellular and molecular events in diabetes mellitus will identify new approaches for therapy. Immune system cells are important modulators of chronic inflammation in diabetes mellitus, but the role of B cells is not adequately studied. The aim of this work was to define the function of B cells in diabetes mellitus patients through focus on B cell responses to pattern recognition receptors.METHODS:
We measured expression and function of Toll-like receptors (TLRs) on peripheral blood B cells from diabetes mellitus patients by flow cytometry and multiplexed cytokine analysis. We similarly analysed B cells from non-diabetic donors and periodontal disease patients as comparative cohorts.RESULTS:
B cells from diabetes mellitus patients secrete multiple pro-inflammatory cytokines, and IL-8 production is significantly elevated in B cells from diabetic patients compared with those from non-diabetic individuals. These data, plus modest elevation of TLR surface expression, suggest B cell IL-8 hyperproduction is a cytokine-specific outcome of altered TLR function in B cells from diabetes mellitus patients. Altered TLR function is further evidenced by demonstration of an unexpected, albeit modest 'anti-inflammatory' function for TLR4. Importantly, B cells from diabetes mellitus patients fail to secrete IL-10, an anti-inflammatory cytokine implicated in inflammatory disease resolution, under a variety of TLR-stimulating conditions. Comparative analyses of B cells from patients with a second chronic inflammatory disease, periodontal disease, indicated that some alterations in B cell TLR function associate specifically with diabetes mellitus. CONCLUSIONS/INTERPRETATION:
Altered TLR function in B cells from diabetes mellitus patients increases inflammation by two mechanisms elevation of pro-inflammatory IL-8 and lack of anti-inflammatory/protective IL-10 production.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Cytokines
/
Diabetes Mellitus
/
Toll-Like Receptors
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Diabetologia
Year:
2010
Type:
Article
Affiliation country:
United States