Hydroxychloroquine efficiently suppresses inflammatory responses of human class-switched memory B cells via Toll-like receptor 9 inhibition

Masataka Torigoe; Kei Sakata; Akina Ishii; Shigeru Iwata; Shingo Nakayamada; Yoshiya Tanaka

doi:10.1016/j.clim.2018.07.003

Hydroxychloroquine efficiently suppresses inflammatory responses of human class-switched memory B cells via Toll-like receptor 9 inhibition

Clin Immunol. 2018 Oct:195:1-7. doi: 10.1016/j.clim.2018.07.003. Epub 2018 Jul 4.

Authors

Masataka Torigoe¹, Kei Sakata², Akina Ishii², Shigeru Iwata³, Shingo Nakayamada³, Yoshiya Tanaka⁴

Affiliations

¹ The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Japan, Kitakyushu 807-8555, Japan; Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu 879-5593, Japan.
² The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Japan, Kitakyushu 807-8555, Japan; Mitsubishi Tanabe Pharma, Yokohama 227-0033, Japan.
³ The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Japan, Kitakyushu 807-8555, Japan.
⁴ The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Japan, Kitakyushu 807-8555, Japan. Electronic address: [email protected].

PMID: 29981383
DOI: 10.1016/j.clim.2018.07.003

Abstract

Hydroxychloroquine is widely used for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Although B cells contribute to the pathogenesis of these diseases, the action of hydroxychloroquine on B cells remains unclear. Here we examined the effects of hydroxychloroquine on functions of B cell subsets. Hydroxychloroquine efficiently inhibited the mammalian target of rapamycin complex 1, differentiation of CD19⁺IgD^-CD27⁺ class-switched memory B cells to plasmablasts and their IgG production, under stimulation with CpG, a Toll-like receptor (TLR)-9 ligand. Hydroxychloroquine also inhibited CpG-induced production of interleukin-6 and tumor necrosis factor-α in B cell subsets. Taken together, hydroxychloroquine markedly suppresses the TLR9-mediated human B cell functions during inflammatory processes. Based on our results, we believe that hydroxychloroquine can be beneficial in the treatment of B cell-mediated autoimmune diseases.

Keywords: Human B cell; Hydroxychloroquine; Plasmablast; Toll-like receptor 9.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents / pharmacology*
Antibody Formation / drug effects
Antigens, CD19 / metabolism
B-Lymphocyte Subsets / immunology*
B-Lymphocytes / immunology*
Cell Differentiation / drug effects
Cells, Cultured
Humans
Hydroxychloroquine / pharmacology*
Immunoglobulin Class Switching
Immunologic Memory
Inflammation / drug therapy*
Interleukin-6 / metabolism
Signal Transduction
TOR Serine-Threonine Kinases / metabolism
Toll-Like Receptor 9 / metabolism*
Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
Tumor Necrosis Factor-alpha / metabolism

Substances

Anti-Inflammatory Agents
Antigens, CD19
Interleukin-6
Toll-Like Receptor 9
Tumor Necrosis Factor Receptor Superfamily, Member 7
Tumor Necrosis Factor-alpha
Hydroxychloroquine
MTOR protein, human
TOR Serine-Threonine Kinases