Narrowband UVB phototherapy reduces TNF production by B-cell subsets stimulated via TLR7 from individuals with early multiple sclerosis

Stephanie Trend; Jonatan Leffler; Matthew N Cooper; Scott N Byrne; Allan G Kermode; Martyn A French; Prue H Hart

doi:10.1002/cti2.1197

Narrowband UVB phototherapy reduces TNF production by B-cell subsets stimulated via TLR7 from individuals with early multiple sclerosis

Clin Transl Immunology. 2020 Oct 15;9(10):e1197. doi: 10.1002/cti2.1197. eCollection 2020.

Authors

Stephanie Trend^{1

2}, Jonatan Leffler¹, Matthew N Cooper¹, Scott N Byrne^{3

4}, Allan G Kermode^{2

5}, Martyn A French⁶, Prue H Hart¹

Affiliations

¹ Telethon Kids Institute University of Western Australia Perth WA Australia.
² Centre for Neuromuscular and Neurological Disorders Perron Institute for Neurological and Translational Science University of Western Australia Perth WA Australia.
³ School of Medical Sciences Faculty of Medicine and Health The University of Sydney Sydney NSW Australia.
⁴ Centre for Immunology and Allergy Research Westmead Institute for Medical Research Westmead NSW Australia.
⁵ Institute for Immunology and Infectious Disease Murdoch University Perth WA Australia.
⁶ UWA Medical School and School of Biomedical Sciences University of Western Australia Perth WA Australia.

Abstract

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.

Keywords: B cells; IL‐10; TLR7; TNF; UVB radiation; multiple sclerosis.