Open AccessNarrowband UVB phototherapy reduces TNF production by B‐cell subsets stimulated via TLR7 from individuals with early multiple sclerosis
Author(s) -
Trend Stephanie,
Leffler Jonatan,
Cooper Matthew N,
Byrne Scott N,
Kermode Allan G,
French Martyn A,
Hart Prue H
Publication year - 2020
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1197
Subject(s) - immunoglobulin d , stimulation , cytokine , tlr7 , medicine , b cell , immunology , tumor necrosis factor alpha , peripheral blood mononuclear cell , endocrinology , biology , immune system , toll like receptor , in vitro , antibody , biochemistry , innate immune system
Objectives At the end of a 60‐day course of narrowband UVB phototherapy, administered to individuals with early multiple sclerosis, there were changes in the relative proportions of circulating B‐cell subsets. This study investigated phototherapy‐associated changes to cytokine responses of B cells when exposed to a TLR7 ligand. Methods PBMCs from participants of the PhoCIS (Phototherapy for Clinically Isolated Syndrome) trial taken before (day 1) and after phototherapy for 8 weeks (day 60) were incubated with, or without, the TLR7 ligand, R848, for 18 h. Production of TNF and IL‐10 in seven B‐cell subsets was examined, with cytokine responses in each individual at day 60, adjusted for responses at day 1. Paired PBMCs were from participants administered phototherapy ( n = 7) or controls ( n = 6). Results At day 60, significantly fewer B cells, particularly marginal zone‐like B cells (CD27 + /IgD + ), from participants administered phototherapy produced TNF in response to TLR7 stimulation. When responses by seven B‐cell subsets were analysed together using multivariate methods, a phototherapy‐specific signature was observed. An increased responsiveness from day 1 to day 60 in IgM‐only memory B cells (CD27 + /IgD − /IgM + ) after TLR7 stimulation also predicted slower progression from CIS to MS. Phototherapy was without significant effect on B‐cell IL‐10 production. Conclusions Reduced TNF responses after TLR7 stimulation in marginal zone‐like B cells from participants administered phototherapy suggested treatment‐associated priming effects that were detected upon subsequent polyclonal B‐cell activation. Changes in responsiveness to TLR7 stimulation also suggested that IgM‐only memory B cells may be important in conversion from CIS to MS.