1. Toll-like receptor signalling in B cells during systemic lupus erythematosus
- Author
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Benoit Manfroi, Simon Fillatreau, and Thomas Dörner
- Subjects
Autoimmune diseases ,Immunology ,Review Article ,Autoantigens ,Mice ,Rheumatology ,Antigen ,immune system diseases ,medicine ,Animals ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,B cell ,Autoantibodies ,Toll-like receptor ,B-Lymphocytes ,Lupus erythematosus ,business.industry ,Effector ,Toll-Like Receptors ,Autoantibody ,TLR9 ,TLR7 ,medicine.disease ,medicine.anatomical_structure ,Toll-Like Receptor 7 ,Toll-Like Receptor 9 ,business ,Signal Transduction - Abstract
B lymphocytes have a central role in autoimmune diseases, which are often defined by specific autoantibody patterns and feature a loss of B cell tolerance. A prototypic disease associated with B cell hyperactivity is systemic lupus erythematosus (SLE). In patients with SLE, the loss of B cell tolerance to autoantigens is controlled in a cell-intrinsic manner by Toll-like receptors (TLRs), which sense nucleic acids in endosomes. TLR7 drives the extrafollicular B cell response and the germinal centre reaction that are involved in autoantibody production and disease pathogenesis. Surprisingly, TLR9 seems to protect against SLE, even though it is required for the production of autoantibodies recognizing double-stranded DNA-associated antigens, which are abundant in SLE and are a hallmark of this disease. The protective function of TLR9 is at least partly mediated by its capacity to limit the stimulatory activity of TLR7. The roles of TLR7 and TLR9 in the effector function of B cells in lupus-like disease and in patients with SLE, and the unique features of TLR signalling in B cells, suggest that targeting TLR signalling in SLE might be therapeutically beneficial., Loss of B cell tolerance to autoantigens in systemic lupus erythematosus (SLE) is driven by TLR7, whereas TLR9 appears to protect against SLE by limiting the stimulatory activity of TLR7. The unique features of Toll-like receptor signalling in B cells implicate it as a therapeutic target in SLE., Key points Intrinsic TLR7 and TLR9 signalling in B cells plays an important role in the development and pathogenesis of systemic lupus erythematosus (SLE).In patients with SLE, effector plasma cells are generated via the extrafollicular response and via the formation of spontaneous germinal centres.TLR7 plays key roles in the extrafollicular response and the response mediated by germinal centres.Some plasma cells produce IL-10 and can have protective roles in lupus-like disease.
- Published
- 2020