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TIM-1 defines a human regulatory B cell population that is altered in frequency and function in systemic sclerosis patients

Aravena, O; Ferrier, A; Menon, M; Mauri, C; Aguillón, JC; Soto, L; Catalán, D; (2017) TIM-1 defines a human regulatory B cell population that is altered in frequency and function in systemic sclerosis patients. Arthritis Research & Therapy , 19 , Article 8. 10.1186/s13075-016-1213-9. Green open access

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Abstract

BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive production of extracellular matrix by fibroblasts on skin and internal organs. Although Th2 cells have been involved in fibroblast stimulation, hyperactivated B cells may also play an important role. Regulatory B cells (Bregs) are cells capable of inhibiting inflammatory responses and controlling autoimmune diseases. Although many Breg populations have in common the ability to produce high amounts of IL-10, a unique surface marker defining most human Bregs is lacking. It has been described in mice that T cell Ig and mucin domain protein 1 (TIM-1) is an inclusive marker for Bregs, and that TIM-1+ B cells are able to prevent the development of autoimmunity. The aim of this work was to evaluate TIM-1 as a marker for human IL-10(+) Bregs, and to determine whether TIM-1+ B cells are defective in SSc patients. METHODS: SSc patients (n = 39) and 53 healthy subjects were recruited. TIM-1 and IL-10 expression was assessed in resting or activated peripheral blood CD19(+) B cells by flow cytometry. The regulatory function of TIM-1(+) or activated B cells from SSc patients and healthy subjects was assessed in autologous and allogenic co-cultures with CD4(+) T cells, where T cell proliferation and IFN-γ, IL-17, TNF-α and IL-4 production by T cells was measured by flow cytometry. RESULTS: TIM-1 and IL-10 were preferentially expressed in transitional B cells, but were upregulated in naïve and memory B cells upon stimulation. The frequency of transitional TIM-1(+) IL-10(+) B cells was significantly decreased in SSc patients compared to healthy controls. In addition, activated B cells from SSc patients induced stronger allogenic Th1 and Th2 responses than activated B cells from healthy controls. Finally, TIM-1(+) B cells, including transitional and non-transitional cells, exhibited a higher CD4(+) T cell suppressive ability than TIM-1(-) B cells in healthy controls, but not in SSc patients. CONCLUSIONS: TIM-1 is a unique marker for the identification of a human IL-10(+) Breg subpopulation which is partially superimposed with transitional B cells. Alterations in TIM-1(+) B cells could contribute to the development of autoimmune diseases such as SSc.

Type: Article
Title: TIM-1 defines a human regulatory B cell population that is altered in frequency and function in systemic sclerosis patients
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13075-016-1213-9
Publisher version: http://dx.doi.org/10.1186/s13075-016-1213-9
Language: English
Additional information: Copyright © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: IL-10, Regulatory B cells, Systemic sclerosis, TIM-1
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/1538681
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