Pathophysiology of cutaneous lupus erythematosus

Abstract

The pathophysiology of cutaneous lupus erythematosus (CLE) encompasses the complex interactions between genetics, the environment, and cells and their products. Recent data have provided enhanced understanding of these interactions and the mechanism by which they cause disease. A number of candidate genes have been identified which increase the risk of developing CLE. Ultraviolet radiation, the predominant environmental exposure associated with CLE, appears to initiate CLE lesion formation by inducing apoptosis, precipitating autoantigen presentation, and promoting cellular production of specific cytokines. Autoantibodies are a well-known entity in CLE, but their exact role remains unclear. Finally, cells ranging from native skin cells to innate and adaptive immune cells produce cytokines and other molecules and play specific roles in lesion formation and perpetuation. Native skin cells implicated in CLE include keratinocytes and endothelial cells. Innate immune cells crucial to CLE pathophysiology include dendritic cells and neutrophils. The primary adaptive immune cells thought to be involved include Th1 cells, Th17 cells, cytotoxic T cells, and invariant natural killer T cells. Though the pathophysiology of CLE has yet to be fully characterized, current research provides direction for future research and therapies.

Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

“…Moreover, TWEAK alone induces the apoptosis of keratinocytes originating from affected skin, which can be exaggerated by TNF-α [8]. The inflammation in cutaneous lupus erythematosus is also predominantly mediated by Th1 cytokines, including interferon-γ and IP-10 [34]. Besides, IL-1, IL-6, IL-17, and TNF-α are also produced in cutaneous lupus erythematosus [34].…”

“…Besides, IL-1, IL-6, IL-17, and TNF-α are also produced in cutaneous lupus erythematosus [34]. Ultraviolet B irradiation induces the keratinocyte release of IL-1 and TNF-α, two primary cytokines in the inflammatory cascade [34]. Ultraviolet B also acts synergistically with IL-1α to promote the production of TNF-α, which can increase its own production in an autocrine manner [34].…”

“…The inflammation in cutaneous lupus erythematosus is also predominantly mediated by Th1 cytokines, including interferon-γ and IP-10 [34]. Besides, IL-1, IL-6, IL-17, and TNF-α are also produced in cutaneous lupus erythematosus [34]. Ultraviolet B irradiation induces the keratinocyte release of IL-1 and TNF-α, two primary cytokines in the inflammatory cascade [34].…”

“…Ultraviolet B also acts synergistically with IL-1α to promote the production of TNF-α, which can increase its own production in an autocrine manner [34]. This cytokine cascade recruits immune cells, exacerbates inflammation, induces the apoptosis of keratinocytes, and ultimately destroys skin tissues, resulting in the photo-induced lesions of cutaneous lupus erythematosus [34]. TWEAK/Fn14 activation is prominent in skin lesions of patients with lupus erythematosus and in MRL/lpr lupus-prone models [11, 31].…”

“…Ultraviolet B irradiation induces the keratinocyte release of IL-1 and TNF-α, two primary cytokines in the inflammatory cascade [34]. Ultraviolet B also acts synergistically with IL-1α to promote the production of TNF-α, which can increase its own production in an autocrine manner [34]. This cytokine cascade recruits immune cells, exacerbates inflammation, induces the apoptosis of keratinocytes, and ultimately destroys skin tissues, resulting in the photo-induced lesions of cutaneous lupus erythematosus [34].…”