Retinoic acid enhances the levels of IL-10 in TLR-stimulated B cells from patients with relapsing–remitting multiple sclerosis

Eriksen, Agnete Bratsberg; Berge, Tone; Gustavsen, Marte Wendel; Leikfoss, Ingvild Sørum; Bos, Steffan D.; Spurkland, Anne; Harbo, Hanne F.; Blomhoff, Heidi Kiil

doi:10.1016/j.jneuroim.2014.11.019

Cited by 21 publications

(25 citation statements)

References 68 publications

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“…The different methods used and heterogeneity in the study cohorts probably explain some of these discrepancies. The Breg cell frequencies observed in MS patient samples were also found to be lower during relapse compared with remission and were normalized during treatment with immunomodulatory drugs . These studies indicate that the ability of Breg cells to produce IL‐10 changes during disease progression, relapse and remission and may affect the severity and progression of MS …”

Section: Introductionmentioning

confidence: 73%

Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis

et al. 2018

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Mouse models of multiple sclerosis (MS) have shown the importance of interleukin-10 (IL-10) -producing regulatory B (Breg) cells in dampening disease activity and inhibiting disease initiation and progression. In MS and other autoimmune diseases decreased frequency and functionality of Breg cells correlate with disease activity and the percentage of IL-10-producing Breg cells decreases during relapse and normalizes in remission. Optic neuritis (ON) is a common first clinical manifestation of MS and IL-10-producing Breg cells may be crucial in the transition from ON to MS, we therefore investigate the frequency and function of Breg cells in ON as a clinical model of early demyelinating disease. B cells were purified from 27 patients with ON sampled close to symptom onset (median 23 days, range 7-41 days) and 13 healthy controls. The B cells were stimulated and cultured for 48 hr with CD40 ligand and CpG before measurement of intracellular IL-10 and the surface markers CD19, CD1d, CD5, CD24, CD38 and CD27 by flow cytometry. The frequency of B-cell subsets was analysed in peripheral blood and cerebral spinal fluid (CSF) of patients. Sixty-five per cent of the IL-10-producing Breg cells co-expressed CD24 and CD38, and only 14% were CD24 high CD27 + , suggesting that the naive B cells are the primary source of IL-10 in the B-cell culture, followed by memory cells in both healthy controls and patients. The frequency of naive CD19 + CD24 + CD38 + Breg cells was higher in patients with ON compared with controls. The ability of Breg cells to produce IL-10 was at normal levels in both ON patients with high risk and those with low risk of progression to MS. We found no correlation between Breg cell function and the presence of brain white matter lesions by magnetic resonance imaging or CSF oligoclonal bands indicative of ON patients carrying a higher risk of conversion to MS. The frequencies of IL-10-producing B cells did not correlate with the conversion to MS at 2-year follow up. Interleukin-10 was primarily produced by naive and memory B cells. The frequency of IL-10secreting B cells did not correlate with risk factors of MS. Breg cell function at clinical onset of ON is not a determining factor for conversion to MS.

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Section: Introductionmentioning

confidence: 73%

Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis

et al. 2018

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“…We and others have demonstrated that RAR stimulation produces anti-inflammatory effects in CNS [13,17]. These effects may be attributable at least in part to regulation of microglial activation [18,19].…”

Section: Introductionmentioning

confidence: 79%

Retinoic acid receptor agonist Am80 inhibits CXCL2 production from microglial BV-2 cells via attenuation of NF-κB signaling

Takaoka

Takahashi

Kurauchi

et al. 2016

International Immunopharmacology

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“…95 BAFF has been shown to induce the proliferation and differentiation of B cells with an antiinflammatory function. 101 Another example is ultraviolet B (UVB) irradiation, which was known to suppress oxazolone-induced CHS in mice via an immune mechanism 102 and has recently been shown to increase numbers of IL-10-expressing B cells, which inhibit T-cell proliferation in CHS. 96 In human, IL-6 and IL-10 secretion by B cells increased after stimulation with BAFF; however, BAFF stimulation alone did not promote B cell-mediated IL-10 secretion.…”

Section: The Immunomodulatory Function Of Il-10 Produced By B Cellsmentioning

confidence: 99%

“…97 There are other mediators that have been shown to induce IL-10 secretion by B cells like alteration in the gut commensal microbiota with antibiotics 98 ; antigen coupled to the B subunit of cholera toxin (CTB), 99 Vitamin D3 (VitD3), 100 and Retinoic Acid in combination with TLR-9 in healthy controls, but not in patients with MS, whom B cells have per se a reduced capacity to secrete IL-10. 101 Another example is ultraviolet B (UVB) irradiation, which was known to suppress oxazolone-induced CHS in mice via an immune mechanism 102 and has recently been shown to increase numbers of IL-10-expressing B cells, which inhibit T-cell proliferation in CHS. 102 Altogether these studies support the idea that there are multiple ways in which IL-10 production by B cells is induced.…”

Section: The Immunomodulatory Function Of Il-10 Produced By B Cellsmentioning

confidence: 99%

Regulatory B cells: Development, phenotypes, functions, and role in transplantation

Alhabbab

Nova‐Lamperti

Aravena

et al. 2019

Immunological Reviews

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The interest in regulatory B cells (Bregs) began in the 1970s with the evidence that B cells could downregulate the immune system by the production of “inhibitory” antibodies. Subsequently, a series of results from different studies have emphasized that B cells have antibody‐independent immunoregulatory functions. Since then, different subsets of B cells with regulatory functions and their development and mechanisms of action have been identified both in human and in animal models of inflammation, transplantation, and autoimmunity. The present review outlines the suggested pathways by which Bregs develop, describes the different subsets of Bregs with their phenotypes and function as well as their role in transplantation, highlighting the differences between human and animal studies throughout.

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Retinoic acid enhances the levels of IL-10 in TLR-stimulated B cells from patients with relapsing–remitting multiple sclerosis

Cited by 21 publications

References 68 publications

Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis

Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis

Retinoic acid receptor agonist Am80 inhibits CXCL2 production from microglial BV-2 cells via attenuation of NF-κB signaling

Regulatory B cells: Development, phenotypes, functions, and role in transplantation

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