Abstract
IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease associated with a break in self-tolerance reflected by a production of antinuclear autoantibodies. Since autoantibody production can be activated via nucleic acid Toll-like receptor 9 (TLR9), the respective pathway has been implicated in the development of SLE and pathogenic B cell responses. However, the response of B cells from SLE patients to TLR9 stimulation remains incompletely characterized.MethodsIn the current study, the response of B cells from SLE patients and healthy donors upon TLR9 stimulation was analyzed in terms of proliferation and cytokine production and correlated with the lupus disease activity and anti-dsDNA titers.ResultsB cells from SLE patients showed a reduced response to TLR9 agonist compared to B cells from healthy donors in terms of proliferation and activation. B cells from SLE patients with higher disease activity produced less interleukin (IL)-6, IL-10, vascular endothelial growth factor, and IL-1ra than B cells from healthy donors. Further analyses revealed an inverse correlation of cytokines produced by TLR9-stimulated B cells with lupus disease activity and anti-dsDNA titer, respectively.ConclusionThe capacity of B cells from lupus patients to produce cytokines upon TLR9 engagement becomes less efficient with increasing disease activity, suggesting that they either enter an exhausted state or become tolerant to TLR stimulation for cytokine production when disease worsens.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0477-1) contains supplementary material, which is available to authorized users.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with a break in self-tolerance reflected by a production of antinuclear autoantibodies
In the current study, a comprehensive analysis was performed to assess the capacity of B cells from SLE patients to respond to toll-like receptor 9 (TLR9) stimulation in terms of proliferation, activation, and cytokine production in relation with clinical lupus activity using SLE disease activity index (SLEDAI)
B cells from SLE patients have a reduced proliferation and activation upon TLR9 stimulation We first evaluated the response of B cells to TLR9 stimulation in terms of proliferation and activation
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with a break in self-tolerance reflected by a production of antinuclear autoantibodies. Since autoantibody production can be activated via nucleic acid Toll-like receptor 9 (TLR9), the respective pathway has been implicated in the development of SLE and pathogenic B cell responses. It has been shown that cytokine production of B cells can be efficiently induced by toll-like receptor (TLR) signaling [17,18,19] In this context, TLR9 is of great interest for SLE immunopathology because increased apoptosis and/or clearance deficiencies in SLE are considered to result in increased amounts of circulating plasma DNA, which may act as TLR agonists and subsequently provide B cell activation signals [20]
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