1. CD24hiCD27+B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide
- Author
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E. Mlejnek, Lucja A. Labuda, Maria Yazdanbakhsh, Hermelijn H. Smits, Pieter S. Hiemstra, M. Janssen Bonas, G.M. Moller, L.E.P.M. van der Vlugt, T. R. Dijksman, Arifa Ozir-Fazalalikhan, Robert Schot, and Bruno Guigas
- Subjects
Adult ,Lipopolysaccharides ,Male ,Allergy ,Lipopolysaccharide ,Regulatory B cells ,Immunology ,B-Lymphocyte Subsets ,Inflammation ,Lymphocyte Activation ,Immunophenotyping ,Young Adult ,chemistry.chemical_compound ,Risk Factors ,T-Lymphocyte Subsets ,medicine ,Humans ,Immunology and Allergy ,human ,Lymphocyte Count ,Receptor ,Asthma ,CD24 ,business.industry ,CD24 Antigen ,Middle Aged ,allergy ,regulatory B cells ,medicine.disease ,Interleukin-10 ,Respiratory Function Tests ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,Toll-Like Receptor 4 ,Interleukin 10 ,Phenotype ,chemistry ,Case-Control Studies ,IL-10 ,Female ,medicine.symptom ,business - Abstract
Background Regulatory B cells have been identified that strongly reduce allergic and auto-immune inflammation in experimental models by producing IL-10. Recently, several human regulatory B-cell subsets with an impaired function in auto-immunity have been described, but there is no information on regulatory B cells in allergic asthma. Objective In this study, the frequency and function of IL-10 producing B-cell subsets in allergic asthma were investigated. Methods Isolated peripheral blood B cells from 13 patients with allergic asthma and matched healthy controls were analyzed for the expression of different regulatory B-cell markers. Next, the B cells were activated by lipopolysaccharide (LPS), CpG or through the B-cell receptor, followed by co-culture with endogenous memory CD4(+) T cells and house dust mite allergen DerP1. Results Lower number of IL-10 producing B cells were found in patients in response to LPS, however, this was not the case when B cells were activated through the B-cell receptor or by CpG. Further dissection showed that only the CD24(hi)CD27(+) B-cell subset was reduced in number and IL-10 production to LPS. In response to DerP1, CD4(+) T cells from patients co-cultured with LPS-primed total B cells produced less IL-10 compared to similar cultures from controls. These results are in line with the finding that sorted CD24(hi)CD27(+) B cells are responsible for the induction of IL-10(+) CD4(+) T cells. Conclusions Taken together, these data indicate that CD24(hi)CD27(+) B cells from allergic asthma patients produce less IL-10 in response to LPS leading to a weaker IL-10 induction in T cells in response to DerP1, which may play a role in allergic asthma.
- Published
- 2014