Towards a pro-resolving concept in systemic lupus erythematosus

Böltz S, Hagen M, Knopf J, Mahajan A, Schick M, Zhao Y, Erfurt-Berge C, Rech J, Munoz Becerra L, Herrmann M (2019)

Publication Type: Journal article, Review article

Publication year: 2019

Journal

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with prominent chronic inflammatory aspects. SLE most often affects women (9:1) in childbearing age. The multifactorial nature of the etiopathogenesis of SLE involves a deficient clearance of dead and dying cells. This is supported by the occurrence of autoantibodies directed against autoantigens modified in dying and dead cells (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e.g., histones H3-K27-me3; H2A/H4 AcK8,12,16; and H2B-AcK12) that are deposited in various tissues, including skin, kidneys, joints, muscles, and brain. The subsequent hyperinflammatory response often leads to irreparable tissue damage and organ destruction. In healthy individuals, dead and dying cells are rapidly removed by macrophages in an anti-inflammatory manner, referred to as efferocytosis. In SLE, extensive and prolonged cell death (apoptosis, necrosis, neutrophil extracellular trap (NET) formation) leads to autoantigens leaking out of the not cleared cell debris. These neo-epitopes are subsequently presented to B cells by follicular dendritic cells in the germinal centers of secondary lymphoid tissues conditioning the break of self-tolerance. Activation of autoreactive B cells and subsequent production of autoantibodies facilitate the formation of immune complexes (ICs) fueling the inflammatory response and leading to further tissue damage. ICs may also be ingested by phagocytes, which then produce further pro-inflammatory cytokines. These processes establish a vicious circle that leads to sustained inflammation. This review highlights the cell death–related events in SLE, the protagonists involved in SLE pathogenesis, the resolution of inflammation in various tissues affected in SLE, and explores strategies for intervention to restore hemostasis in a hyperinflammatory state.

Authors with CRIS profile

Sebastian Böltz Lehrstuhl für Biochemie und Molekulare Medizin Melanie Hagen Department of Medicine 3 – Rheumatology and Immunology Jasmin Knopf Department of Medicine 3 – Rheumatology and Immunology Aparna Mahajan Department of Medicine 3 – Rheumatology and Immunology Maximilian Schick Medizinische Fakultät Cornelia Erfurt-Berge Department of Dermatology Hans Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology

How to cite

APA:

Böltz, S., Hagen, M., Knopf, J., Mahajan, A., Schick, M., Zhao, Y.,... Herrmann, M. (2019). Towards a pro-resolving concept in systemic lupus erythematosus. Seminars in Immunopathology. https://doi.org/10.1007/s00281-019-00760-5

MLA:

Böltz, Sebastian, et al. "Towards a pro-resolving concept in systemic lupus erythematosus." Seminars in Immunopathology (2019).

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